Coevolutionary modeling in network formation

KAUST Repository

Al-Shyoukh, Ibrahim; Chasparis, Georgios; Shamma, Jeff S.

2014-01-01

Network coevolution, the process of network topology evolution in feedback with dynamical processes over the network nodes, is a common feature of many engineered and natural networks. In such settings, the change in network topology occurs at a comparable time scale to nodal dynamics. Coevolutionary modeling offers the possibility to better understand how and why network structures emerge. For example, social networks can exhibit a variety of structures, ranging from almost uniform to scale-free degree distributions. While current models of network formation can reproduce these structures, coevolutionary modeling can offer a better understanding of the underlying dynamics. This paper presents an overview of recent work on coevolutionary models of network formation, with an emphasis on the following three settings: (i) dynamic flow of benefits and costs, (ii) transient link establishment costs, and (iii) latent preferential attachment.

Network Formation under the Threat of Disruption

NARCIS (Netherlands)

Hoyer, B.

2013-01-01

The studies in this thesis are focused on the impact the presence of a network disruptor has on network formation models. In particular, we build two theoretical models to study the effect of network disruption on network formation and test the effect network disruption has on equilibrium selection

Domains I and IV of annexin A2 affect the formation and integrity of in vitro capillary-like networks.

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Aase M Raddum

Full Text Available Annexin A2 (AnxA2 is a widely expressed multifunctional protein found in different cellular compartments. In spite of lacking a hydrophobic signal peptide, AnxA2 is found at the cell surface of endothelial cells, indicative of a role in angiogenesis. Increased extracellular levels of AnxA2 in tumours correlate with neoangiogenesis, metastasis and poor prognosis. We hypothesised that extracellular AnxA2 may contribute to angiogenesis by affecting endothelial cell-cell interactions and motility. To address this question, we studied the effect of heterotetrameric and monomeric forms of AnxA2, as well as its two soluble domains on the formation and maintenance of capillary-like structures by using an in vitro co-culture system consisting of endothelial and smooth muscle cells. In particular, addition of purified domains I and IV of AnxA2 potently inhibited the vascular endothelial growth factor (VEGF-dependent formation of the capillary-like networks in a dose-dependent manner. In addition, these AnxA2 domains disrupted endothelial cell-cell contacts in preformed capillary-like networks, resulting in the internalisation of vascular endothelial (VE-cadherin and the formation of VE-cadherin-containing filopodia-like structures between the endothelial cells, suggesting increased cell motility. Addition of monoclonal AnxA2 antibodies, in particular against Tyr23 phosphorylated AnxA2, also strongly inhibited network formation in the co-culture system. These results suggest that extracellular AnxA2, most likely in its Tyr phosphorylated form, plays a pivotal role in angiogenesis. The exogenously added AnxA2 domains most likely mediate their effects by competing with endogenous AnxA2 for extracellular factors necessary for the initiation and maintenance of angiogenesis, such as those involved in the formation/integrity of cell-cell contacts.

Bioprinting for vascular and vascularized tissue biofabrication.

Science.gov (United States)

Datta, Pallab; Ayan, Bugra; Ozbolat, Ibrahim T

2017-03-15

Bioprinting is a promising technology to fabricate design-specific tissue constructs due to its ability to create complex, heterocellular structures with anatomical precision. Bioprinting enables the deposition of various biologics including growth factors, cells, genes, neo-tissues and extra-cellular matrix-like hydrogels. Benefits of bioprinting have started to make a mark in the fields of tissue engineering, regenerative medicine and pharmaceutics. Specifically, in the field of tissue engineering, the creation of vascularized tissue constructs has remained a principal challenge till date. However, given the myriad advantages over other biofabrication methods, it becomes organic to expect that bioprinting can provide a viable solution for the vascularization problem, and facilitate the clinical translation of tissue engineered constructs. This article provides a comprehensive account of bioprinting of vascular and vascularized tissue constructs. The review is structured as introducing the scope of bioprinting in tissue engineering applications, key vascular anatomical features and then a thorough coverage of 3D bioprinting using extrusion-, droplet- and laser-based bioprinting for fabrication of vascular tissue constructs. The review then provides the reader with the use of bioprinting for obtaining thick vascularized tissues using sacrificial bioink materials. Current challenges are discussed, a comparative evaluation of different bioprinting modalities is presented and future prospects are provided to the reader. Biofabrication of living tissues and organs at the clinically-relevant volumes vitally depends on the integration of vascular network. Despite the great progress in traditional biofabrication approaches, building perfusable hierarchical vascular network is a major challenge. Bioprinting is an emerging technology to fabricate design-specific tissue constructs due to its ability to create complex, heterocellular structures with anatomical precision

Ethylene-Related Gene Expression Networks in Wood Formation

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Carolin Seyfferth

2018-03-01

Full Text Available Thickening of tree stems is the result of secondary growth, accomplished by the meristematic activity of the vascular cambium. Secondary growth of the stem entails developmental cascades resulting in the formation of secondary phloem outwards and secondary xylem (i.e., wood inwards of the stem. Signaling and transcriptional reprogramming by the phytohormone ethylene modifies cambial growth and cell differentiation, but the molecular link between ethylene and secondary growth remains unknown. We addressed this shortcoming by analyzing expression profiles and co-expression networks of ethylene pathway genes using the AspWood transcriptome database which covers all stages of secondary growth in aspen (Populus tremula stems. ACC synthase expression suggests that the ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC is synthesized during xylem expansion and xylem cell maturation. Ethylene-mediated transcriptional reprogramming occurs during all stages of secondary growth, as deduced from AspWood expression profiles of ethylene-responsive genes. A network centrality analysis of the AspWood dataset identified EIN3D and 11 ERFs as hubs. No overlap was found between the co-expressed genes of the EIN3 and ERF hubs, suggesting target diversification and hence independent roles for these transcription factor families during normal wood formation. The EIN3D hub was part of a large co-expression gene module, which contained 16 transcription factors, among them several new candidates that have not been earlier connected to wood formation and a VND-INTERACTING 2 (VNI2 homolog. We experimentally demonstrated Populus EIN3D function in ethylene signaling in Arabidopsis thaliana. The ERF hubs ERF118 and ERF119 were connected on the basis of their expression pattern and gene co-expression module composition to xylem cell expansion and secondary cell wall formation, respectively. We hereby establish data resources for ethylene-responsive genes and

Stem Cells on Biomaterials for Synthetic Grafts to Promote Vascular Healing

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Babczyk, Patrick; Conzendorf, Clelia; Klose, Jens; Schulze, Margit; Harre, Kathrin; Tobiasch, Edda

2014-01-01

This review is divided into two interconnected parts, namely a biological and a chemical one. The focus of the first part is on the biological background for constructing tissue-engineered vascular grafts to promote vascular healing. Various cell types, such as embryonic, mesenchymal and induced pluripotent stem cells, progenitor cells and endothelial- and smooth muscle cells will be discussed with respect to their specific markers. The in vitro and in vivo models and their potential to treat vascular diseases are also introduced. The chemical part focuses on strategies using either artificial or natural polymers for scaffold fabrication, including decellularized cardiovascular tissue. An overview will be given on scaffold fabrication including conventional methods and nanotechnologies. Special attention is given to 3D network formation via different chemical and physical cross-linking methods. In particular, electron beam treatment is introduced as a method to combine 3D network formation and surface modification. The review includes recently published scientific data and patents which have been registered within the last decade. PMID:26237251

Progressively Disrupted Brain Functional Connectivity Network in Subcortical Ischemic Vascular Cognitive Impairment Patients.

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Sang, Linqiong; Chen, Lin; Wang, Li; Zhang, Jingna; Zhang, Ye; Li, Pengyue; Li, Chuanming; Qiu, Mingguo

2018-01-01

Cognitive impairment caused by subcortical ischemic vascular disease (SIVD) has been elucidated by many neuroimaging studies. However, little is known regarding the changes in brain functional connectivity networks in relation to the severity of cognitive impairment in SIVD. In the present study, 20 subcortical ischemic vascular cognitive impairment no dementia patients (SIVCIND) and 20 dementia patients (SIVaD) were enrolled; additionally, 19 normal controls were recruited. Each participant underwent a resting-state functional MRI scan. Whole-brain functional networks were analyzed with graph theory and network-based statistics (NBS) to study the functional organization of networks and find alterations in functional connectivity among brain regions. After adjustments for age, gender, and duration of formal education, there were significant group differences for two network functional organization indices, global efficiency and local efficiency, which decreased (NC > SIVCIND > SIVaD) as cognitive impairment worsened. Between-group differences in functional connectivity (NBS corrected, p  impairment worsened, with an increased number of decreased connections between brain regions. We also observed more reductions in nodal efficiency in the prefrontal and temporal cortices for SIVaD than for SIVCIND. These findings indicated a progressively disrupted pattern of the brain functional connectivity network with increased cognitive impairment and showed promise for the development of reliable biomarkers of network metric changes related to cognitive impairment caused by SIVD.

PolNet: A Tool to Quantify Network-Level Cell Polarity and Blood Flow in Vascular Remodeling.

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Bernabeu, Miguel O; Jones, Martin L; Nash, Rupert W; Pezzarossa, Anna; Coveney, Peter V; Gerhardt, Holger; Franco, Claudio A

2018-05-08

In this article, we present PolNet, an open-source software tool for the study of blood flow and cell-level biological activity during vessel morphogenesis. We provide an image acquisition, segmentation, and analysis protocol to quantify endothelial cell polarity in entire in vivo vascular networks. In combination, we use computational fluid dynamics to characterize the hemodynamics of the vascular networks under study. The tool enables, to our knowledge for the first time, a network-level analysis of polarity and flow for individual endothelial cells. To date, PolNet has proven invaluable for the study of endothelial cell polarization and migration during vascular patterning, as demonstrated by two recent publications. Additionally, the tool can be easily extended to correlate blood flow with other experimental observations at the cellular/molecular level. We release the source code of our tool under the Lesser General Public License. Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Protocol for Communication Networking for Formation Flying

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Jennings, Esther; Okino, Clayton; Gao, Jay; Clare, Loren

2009-01-01

An application-layer protocol and a network architecture have been proposed for data communications among multiple autonomous spacecraft that are required to fly in a precise formation in order to perform scientific observations. The protocol could also be applied to other autonomous vehicles operating in formation, including robotic aircraft, robotic land vehicles, and robotic underwater vehicles. A group of spacecraft or other vehicles to which the protocol applies could be characterized as a precision-formation- flying (PFF) network, and each vehicle could be characterized as a node in the PFF network. In order to support precise formation flying, it would be necessary to establish a corresponding communication network, through which the vehicles could exchange position and orientation data and formation-control commands. The communication network must enable communication during early phases of a mission, when little positional knowledge is available. Particularly during early mission phases, the distances among vehicles may be so large that communication could be achieved only by relaying across multiple links. The large distances and need for omnidirectional coverage would limit communication links to operation at low bandwidth during these mission phases. Once the vehicles were in formation and distances were shorter, the communication network would be required to provide high-bandwidth, low-jitter service to support tight formation-control loops. The proposed protocol and architecture, intended to satisfy the aforementioned and other requirements, are based on a standard layered-reference-model concept. The proposed application protocol would be used in conjunction with conventional network, data-link, and physical-layer protocols. The proposed protocol includes the ubiquitous Institute of Electrical and Electronics Engineers (IEEE) 802.11 medium access control (MAC) protocol to be used in the datalink layer. In addition to its widespread and proven use in

Social network composition of vascular patients and its associations with health behavior and clinical risk factors.

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Naomi Heijmans

Full Text Available This study aimed to explore linkages of patients' social network composition with health behaviors and clinical risk factors.This observational study was embedded in a project aimed at improving cardiovascular risk management (CRVM in primary care. 657 vascular patients (227 with cardiovascular disease, 380 at high vascular risk, mean age 72.4 (SD 9.4 years, were recruited as were individuals patients considered important for dealing with their disease, so called alters (n = 487. Network composition was measured with structured patient questionnaires. Both patients and alters completed questionnaires to measure health behavior (habits for physical activity, diet, and smoking. Clinical risk factors (systolic blood pressure, LDL cholesterol level, and body mass index were extracted from patients' medical records. Six logistic regression analyses, using generalized estimating equations, were used to test three hypothesized effects of network composition (having alters with healthful behaviors, without depression, and with specialized knowledge on six outcomes, adjusted for demographic, personal and psychological characteristics.Having alters with overall healthful behavior was related to healthful patient diet (OR 2.14, 95%CI: 1.52-3.02. Having non-smoking alters in networks was related to reduced odds for patient smoking (OR 0.17, 95%CI: 0.05-0.60. No effects of presence of non-depressed alters were found. Presence of alters with specialized knowledge on CVRM was inversely related to healthful diet habits of patients (OR 0.47, 95%CI 0.24-0.89. No significant associations between social network composition and clinical risk factors were found.Diet and smoking, but not physical exercise and clinical risk factors, were associated with social network composition of patients with vascular conditions. In this study of vascular patients, controlling for both personal and psychological factors, fewer network influences were found compared to previous

Strategies in Interventional Radiology: Formation of an Interdisciplinary Center of Vascular Anomalies - Chances and Challenges for Effective and Efficient Patient Management.

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Sadick, Maliha; Dally, Franz Josef; Schönberg, Stefan O; Stroszczynski, Christian; Wohlgemuth, Walter A

2017-10-01

Background  Radiology is an interdisciplinary field dedicated to the diagnosis and treatment of numerous diseases and is involved in the development of multimodal treatment concepts. Method  Interdisciplinary case management, a broad spectrum of diagnostic imaging facilities and dedicated endovascular radiological treatment options are valuable tools that allow radiology to set up an interdisciplinary center for vascular anomalies. Results  Image-based diagnosis combined with endovascular treatment options is an essential tool for the treatment of patients with highly complex vascular diseases. These vascular anomalies can affect numerous parts of the body so that a multidisciplinary treatment approach is required for optimal patient care. Conclusion  This paper discusses the possibilities and challenges regarding effective and efficient patient management in connection with the formation of an interdisciplinary center for vascular anomalies with strengthening of the clinical role of radiologists. Key points   · Vascular anomalies, which include vascular tumors and malformations, are complex to diagnose and treat.. · There are far more patients with vascular anomalies requiring therapy than interdisciplinary centers for vascular anomalies - there is currently a shortage of dedicated interdisciplinary centers for vascular anomalies in Germany that can provide dedicated care for affected patients.. · Radiology includes a broad spectrum of diagnostic and minimally invasive therapeutic tools which allow the formation of an interdisciplinary center for vascular anomalies for effective, efficient and comprehensive patient management.. Citation Format · Sadick M, Dally FJ, Schönberg SO et al. Strategies in Interventional Radiology: Formation of an Interdisciplinary Center of Vascular Anomalies - Chances and Challenges for Effective and Efficient Patient Management. Fortschr Röntgenstr 2017; 189: 957 - 966. © Georg Thieme Verlag KG Stuttgart · New

Molecular biology of breast cancer metastasis Molecular expression of vascular markers by aggressive breast cancer cells

International Nuclear Information System (INIS)

Hendrix, Mary JC; Seftor, Elisabeth A; Kirschmann, Dawn A; Seftor, Richard EB

2000-01-01

During embryogenesis, the formation of primary vascular networks occurs via the processes of vasculogenesis and angiogenesis. In uveal melanoma, vasculogenic mimicry describes the 'embryonic-like' ability of aggressive, but not nonaggressive, tumor cells to form networks surrounding spheroids of tumor cells in three-dimensional culture; these recapitulate the patterned networks seen in patients' aggressive tumors and correlates with poor prognosis. The molecular profile of these aggressive tumor cells suggests that they have a deregulated genotype, capable of expressing vascular phenotypes. Similarly, the embryonic-like phenotype expressed by the aggressive human breast cancer cells is associated with their ability to express a variety of vascular markers. These studies may offer new insights for consideration in breast cancer diagnosis and therapeutic intervention strategies

Bioengineering vascularized tissue constructs using an injectable cell-laden enzymatically crosslinked collagen hydrogel derived from dermal extracellular matrix.

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Kuo, Kuan-Chih; Lin, Ruei-Zeng; Tien, Han-Wen; Wu, Pei-Yun; Li, Yen-Cheng; Melero-Martin, Juan M; Chen, Ying-Chieh

2015-11-01

Tissue engineering promises to restore or replace diseased or damaged tissue by creating functional and transplantable artificial tissues. The development of artificial tissues with large dimensions that exceed the diffusion limitation will require nutrients and oxygen to be delivered via perfusion instead of diffusion alone over a short time period. One approach to perfusion is to vascularize engineered tissues, creating a de novo three-dimensional (3D) microvascular network within the tissue construct. This significantly shortens the time of in vivo anastomosis, perfusion and graft integration with the host. In this study, we aimed to develop injectable allogeneic collagen-phenolic hydroxyl (collagen-Ph) hydrogels that are capable of controlling a wide range of physicochemical properties, including stiffness, water absorption and degradability. We tested whether collagen-Ph hydrogels could support the formation of vascularized engineered tissue graft by human blood-derived endothelial colony-forming cells (ECFCs) and bone marrow-derived mesenchymal stem cells (MSC) in vivo. First, we studied the growth of adherent ECFCs and MSCs on or in the hydrogels. To examine the potential formation of functional vascular networks in vivo, a liquid pre-polymer solution of collagen-Ph containing human ECFCs and MSCs, horseradish peroxidase and hydrogen peroxide was injected into the subcutaneous space or abdominal muscle defect of an immunodeficient mouse before gelation, to form a 3D cell-laden polymerized construct. These results showed that extensive human ECFC-lined vascular networks can be generated within 7 days, the engineered vascular density inside collagen-Ph hydrogel constructs can be manipulated through refinable mechanical properties and proteolytic degradability, and these networks can form functional anastomoses with the existing vasculature to further support the survival of host muscle tissues. Finally, optimized conditions of the cell-laden collagen

Mechanisms of lumen formation during sprouting angiogenesis in vivo

OpenAIRE

Gebala, V. M.

2016-01-01

During development, vascular networks expand following a process known as sprouting angiogenesis. New vascular branches arise from pre-existing vessels through the coordinated migration and proliferation of endothelial cells, and eventually connect to form new vascular loops. The functionality of these new vessel segments is dependent on the opening of a central lumen to allow perfusion. While mechanisms of lumen formation during the establishment of the primary vasculature by vasculogenesis ...

Consensus formation on coevolving networks: groups' formation and structure

International Nuclear Information System (INIS)

Kozma, Balazs; Barrat, Alain

2008-01-01

We study the effect of adaptivity on a social model of opinion dynamics and consensus formation. We analyse how the adaptivity of the network of contacts between agents to the underlying social dynamics affects the size and topological properties of groups and the convergence time to the stable final state. We find that, while on static networks these properties are determined by percolation phenomena, on adaptive networks the rewiring process leads to different behaviors: adaptive rewiring fosters group formation by enhancing communication between agents of similar opinion, though it also makes possible the division of clusters. We show how the convergence time is determined by the characteristic time of link rearrangement. We finally investigate how the adaptivity yields nontrivial correlations between the internal topology and the size of the groups of agreeing agents

A biodegradable vascularizing membrane: a feasibility study.

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Kaushiva, Anchal; Turzhitsky, Vladimir M; Darmoc, Marissa; Backman, Vadim; Ameer, Guillermo A

2007-09-01

Regenerative medicine and in vivo biosensor applications require the formation of mature vascular networks for long-term success. This study investigated whether biodegradable porous membranes could induce the formation of a vascularized fibrous capsule and, if so, the effect of degradation kinetics on neovascularization. Poly(l-lactic acid) (PLLA) and poly(dl-lactic-co-glycolic) acid (PLGA) membranes were created by a solvent casting/salt leaching method. Specifically, PLLA, PLGA 75:25 and PLGA 50:50 polymers were used to vary degradation kinetics. The membranes were designed to have an average 60mum pore diameter, as this pore size has been shown to be optimal for inducing blood vessel formation around nondegradable polymer materials. Membrane samples were imaged by scanning electron microscopy at several time points during in vitro degradation to assess any changes in pore structure. The in vivo performance of the membranes was assessed in Sprague-Dawley rats by measuring vascularization within the fibrous capsule that forms adjacent to implants. The vascular density within 100microm of the membranes was compared with that seen in normal tissue, and to that surrounding the commercially available vascularizing membrane TheraCyte. The hemoglobin content of tissue containing the membranes was measured by four-dimensional elastic light scattering as a novel method to assess tissue perfusion. Results from this study show that slow-degrading membranes induce greater amounts of neovascularization and a thinner fibrous capsule relative to fast degrading membranes. These results may be due both to an initially increased number of macrophages surrounding the slower degrading membranes and to the maintenance of their initial pore structure.

The Role of Trust in Costly Network Formation

NARCIS (Netherlands)

Gilles, R.P.; Sarangi, S.

2003-01-01

We consider game theoretic models of social network formation.In this paper we limit our investigation to game theoretic models of network formation that are based on individual actions only.Our approach is based on three simple and realistic principles: (1) Link formation is a binary process of

Vascular and micro-environmental influences on MSC-coral hydroxyapatite construct-based bone tissue engineering.

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Cai, Lei; Wang, Qian; Gu, Congmin; Wu, Jingguo; Wang, Jian; Kang, Ning; Hu, Jiewei; Xie, Fang; Yan, Li; Liu, Xia; Cao, Yilin; Xiao, Ran

2011-11-01

Bone tissue engineering (BTE) has been demonstrated an effective approach to generate bone tissue and repair bone defect in ectopic and orthotopic sites. The strategy of using a prevascularized tissue-engineered bone grafts (TEBG) fabricated ectopically to repair bone defects, which is called live bone graft surgery, has not been reported. And the quantitative advantages of vascularization and osteogenic environment in promoting engineered bone formation have not been defined yet. In the current study we generated a tissue engineered bone flap with a vascular pedicle of saphenous arteriovenous in which an organized vascular network was observed after 4 weeks implantation, and followed by a successful repaire of fibular defect in beagle dogs. Besides, after a 9 months long term observation of engineered bone formation in ectopic and orthotopic sites, four CHA (coral hydroxyapatite) scaffold groups were evaluated by CT (computed tomography) analysis. By the comparison of bone formation and scaffold degradation between different groups, the influences of vascularization and micro-environment on tissue engineered bone were quantitatively analyzed. The results showed that in the first 3 months vascularization improved engineered bone formation by 2 times of non-vascular group and bone defect micro-environment improved it by 3 times of ectopic group, and the CHA-scaffold degradation was accelerated as well. Copyright © 2011 Elsevier Ltd. All rights reserved.

Vascular endothelial growth factor modified macrophages transdifferentiate into endothelial-like cells and decrease foam cell formation.

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Yan, Dan; He, Yujuan; Dai, Jun; Yang, Lili; Wang, Xiaoyan; Ruan, Qiurong

2017-06-30

Macrophages are largely involved in the whole process of atherosclerosis from an initiation lesion to an advanced lesion. Endothelial disruption is the initial step and macrophage-derived foam cells are the hallmark of atherosclerosis. Promotion of vascular integrity and inhibition of foam cell formation are two important strategies for preventing atherosclerosis. How can we inhibit even the reverse negative role of macrophages in atherosclerosis? The present study was performed to investigate if overexpressing endogenous human vascular endothelial growth factor (VEGF) could facilitate transdifferentiation of macrophages into endothelial-like cells (ELCs) and inhibit foam cell formation. We demonstrated that VEGF-modified macrophages which stably overexpressed human VEGF (hVEGF 165 ) displayed a high capability to alter their phenotype and function into ELCs in vitro Exogenous VEGF could not replace endogenous VEGF to induce the transdifferentiation of macrophages into ELCs in vitro We further showed that VEGF-modified macrophages significantly decreased cytoplasmic lipid accumulation after treatment with oxidized LDL (ox-LDL). Moreover, down-regulation of CD36 expression in these cells was probably one of the mechanisms of reduction in foam cell formation. Our results provided the in vitro proof of VEGF-modified macrophages as atheroprotective therapeutic cells by both promotion of vascular repair and inhibition of foam cell formation. © 2017 The Author(s).

Networks for Autonomous Formation Flying Satellite Systems

Science.gov (United States)

Knoblock, Eric J.; Konangi, Vijay K.; Wallett, Thomas M.; Bhasin, Kul B.

2001-01-01

The performance of three communications networks to support autonomous multi-spacecraft formation flying systems is presented. All systems are comprised of a ten-satellite formation arranged in a star topology, with one of the satellites designated as the central or "mother ship." All data is routed through the mother ship to the terrestrial network. The first system uses a TCP/lP over ATM protocol architecture within the formation the second system uses the IEEE 802.11 protocol architecture within the formation and the last system uses both of the previous architectures with a constellation of geosynchronous satellites serving as an intermediate point-of-contact between the formation and the terrestrial network. The simulations consist of file transfers using either the File Transfer Protocol (FTP) or the Simple Automatic File Exchange (SAFE) Protocol. The results compare the IF queuing delay, and IP processing delay at the mother ship as well as application-level round-trip time for both systems, In all cases, using IEEE 802.11 within the formation yields less delay. Also, the throughput exhibited by SAFE is better than FTP.

PageRank model of opinion formation on Ulam networks

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Chakhmakhchyan, L.; Shepelyansky, D.

2013-12-01

We consider a PageRank model of opinion formation on Ulam networks, generated by the intermittency map and the typical Chirikov map. The Ulam networks generated by these maps have certain similarities with such scale-free networks as the World Wide Web (WWW), showing an algebraic decay of the PageRank probability. We find that the opinion formation process on Ulam networks has certain similarities but also distinct features comparing to the WWW. We attribute these distinctions to internal differences in network structure of the Ulam and WWW networks. We also analyze the process of opinion formation in the frame of generalized Sznajd model which protects opinion of small communities.

Stages of neuronal network formation

International Nuclear Information System (INIS)

Woiterski, Lydia; Käs, Josef A; Claudepierre, Thomas; Luxenhofer, Robert; Jordan, Rainer

2013-01-01

Graph theoretical approaches have become a powerful tool for investigating the architecture and dynamics of complex networks. The topology of network graphs revealed small-world properties for very different real systems among these neuronal networks. In this study, we observed the early development of mouse retinal ganglion cell (RGC) networks in vitro using time-lapse video microscopy. By means of a time-resolved graph theoretical analysis of the connectivity, shortest path length and the edge length, we were able to discover the different stages during the network formation. Starting from single cells, at the first stage neurons connected to each other ending up in a network with maximum complexity. In the further course, we observed a simplification of the network which manifested in a change of relevant network parameters such as the minimization of the path length. Moreover, we found that RGC networks self-organized as small-world networks at both stages; however, the optimization occurred only in the second stage. (paper)

Printing continuously graded interpenetrating polymer networks of acrylate/epoxy by manipulating cationic network formation during stereolithography

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W. Li

2016-12-01

Full Text Available Ultra-violet (UV laser assisted stereolithography is used to print graded interpenetrating polymer networks (IPNs by controlling network formation. Unlike the traditional process where structural change in IPNs is achieved by varying the feeding ratio of monomers or polymer precursors, in this demonstration property is changed by controlled termination of network formation. A photo-initiated process is used to construct IPNs by a combination of radical and cationic network formation in an acrylate/epoxy system. The extent of the cationic network formation is used to control the final properties of the system. Rapid-Scan Fourier Transformation Infrared Spectroscopy (RS-FTIR is used to track the curing kinetics of the two networks and identify key parameters to control the final properties. Atomic force microscopy (AFM and differential scanning calorimetry (DSC confirm the formation of homogenous IPNs, whereas nano-indentation indicates that properties vary with the extent of cationic network formation. The curing characteristics are used to design and demonstrate printing of graded IPNs that show two orders of magnitude variation in mechanical properties in the millimeter scale.

Optical coherence tomography angiography retinal vascular network assessment in multiple sclerosis.

Science.gov (United States)

Lanzillo, Roberta; Cennamo, Gilda; Criscuolo, Chiara; Carotenuto, Antonio; Velotti, Nunzio; Sparnelli, Federica; Cianflone, Alessandra; Moccia, Marcello; Brescia Morra, Vincenzo

2017-09-01

Optical coherence tomography (OCT) angiography is a new method to assess the density of the vascular networks. Vascular abnormalities are considered involved in multiple sclerosis (MS) pathology. To assess the presence of vascular abnormalities in MS and to evaluate their correlation to disease features. A total of 50 MS patients with and without history of optic neuritis (ON) and 46 healthy subjects were included. All underwent spectral domain (SD)-OCT and OCT angiography. Clinical history, Expanded Disability Status Scale (EDSS), Multiple Sclerosis Severity Score (MSSS) and disease duration were collected. Angio-OCT showed a vessel density reduction in eyes of MS patients when compared to controls. A statistically significant reduction in all SD-OCT and OCT angiography parameters was noticed both in eyes with and without ON when compared with control eyes. We found an inverse correlation between SD-OCT parameters and MSSS ( p = 0.003) and between vessel density parameters and EDSS ( p = 0.007). We report a vessel density reduction in retina of MS patients. We highlight the clinical correlation between vessel density and EDSS, suggesting that angio-OCT could be a good marker of disease and of disability in MS.

Assembly and patterning of the vascular network of the vertebrate hindbrain

OpenAIRE

Fujita, Misato; Cha, Young R.; Pham, Van N.; Sakurai, Atsuko; Roman, Beth L.; Gutkind, J. Silvio; Weinstein, Brant M.

2011-01-01

The cranial vasculature is essential for the survival and development of the central nervous system and is important in stroke and other brain pathologies. Cranial vessels form in a reproducible and evolutionarily conserved manner, but the process by which these vessels assemble and acquire their stereotypic patterning remains unclear. Here, we examine the stepwise assembly and patterning of the vascular network of the zebrafish hindbrain. The major artery supplying the hindbrain, the basilar...

Network Configuration Analysis for Formation Flying Satellites

Science.gov (United States)

Knoblock, Eric J.; Wallett, Thomas M.; Konangi, Vijay K.; Bhasin, Kul B.

2001-01-01

The performance of two networks to support autonomous multi-spacecraft formation flying systems is presented. Both systems are comprised of a ten-satellite formation, with one of the satellites designated as the central or 'mother ship.' All data is routed through the mother ship to the terrestrial network. The first system uses a TCP/EP over ATM protocol architecture within the formation, and the second system uses the IEEE 802.11 protocol architecture within the formation. The simulations consist of file transfers using either the File Transfer Protocol (FTP) or the Simple Automatic File Exchange (SAFE) Protocol. The results compare the IP queuing delay, IP queue size and IP processing delay at the mother ship as well as end-to-end delay for both systems. In all cases, using IEEE 802.11 within the formation yields less delay. Also, the throughput exhibited by SAFE is better than FTP.

In vitro model of vascularized bone: synergizing vascular development and osteogenesis.

Directory of Open Access Journals (Sweden)

Cristina Correia

Full Text Available Tissue engineering provides unique opportunities for regenerating diseased or damaged tissues using cells obtained from tissue biopsies. Tissue engineered grafts can also be used as high fidelity models to probe cellular and molecular interactions underlying developmental processes. In this study, we co-cultured human umbilical vein endothelial cells (HUVECs and human mesenchymal stem cells (MSCs under various environmental conditions to elicit synergistic interactions leading to the colocalized development of capillary-like and bone-like tissues. Cells were encapsulated at the 1:1 ratio in fibrin gel to screen compositions of endothelial growth medium (EGM and osteogenic medium (OM. It was determined that, to form both tissues, co-cultures should first be supplied with EGM followed by a 1:1 cocktail of the two media types containing bone morphogenetic protein-2. Subsequent studies of HUVECs and MSCs cultured in decellularized, trabecular bone scaffolds for 6 weeks assessed the effects on tissue construct of both temporal variations in growth-factor availability and addition of fresh cells. The resulting grafts were implanted subcutaneously into nude mice to determine the phenotype stability and functionality of engineered vessels. Two important findings resulted from these studies: (i vascular development needs to be induced prior to osteogenesis, and (ii the addition of additional hMSCs at the osteogenic induction stage improves both tissue outcomes, as shown by increased bone volume fraction, osteoid deposition, close proximity of bone proteins to vascular networks, and anastomosis of vascular networks with the host vasculature. Interestingly, these observations compare well with what has been described for native development. We propose that our cultivation system can mimic various aspects of endothelial cell-osteogenic precursor interactions in vivo, and could find utility as a model for studies of heterotypic cellular interactions that

Vascular Endothelial Growth Factor Sequestration Enhances In Vivo Cartilage Formation

Directory of Open Access Journals (Sweden)

Carolina M. Medeiros Da Cunha

2017-11-01

Full Text Available Autologous chondrocyte transplantation for cartilage repair still has unsatisfactory clinical outcomes because of inter-donor variability and poor cartilage quality formation. Re-differentiation of monolayer-expanded human chondrocytes is not easy in the absence of potent morphogens. The Vascular Endothelial Growth Factor (VEGF plays a master role in angiogenesis and in negatively regulating cartilage growth by stimulating vascular invasion and ossification. Therefore, we hypothesized that its sole microenvironmental blockade by either VEGF sequestration by soluble VEGF receptor-2 (Flk-1 or by antiangiogenic hyperbranched peptides could improve chondrogenesis of expanded human nasal chondrocytes (NC freshly seeded on collagen scaffolds. Chondrogenesis of several NC donors was assessed either in vitro or ectopically in nude mice. VEGF blockade appeared not to affect NC in vitro differentiation, whereas it efficiently inhibited blood vessel ingrowth in vivo. After 8 weeks, in vivo glycosaminoglycan deposition was approximately two-fold higher when antiangiogenic approaches were used, as compared to the control group. Our data indicates that the inhibition of VEGF signaling, independently of the specific implementation mode, has profound effects on in vivo NC chondrogenesis, even in the absence of chondroinductive signals during prior culture or at the implantation site.

Bump formation in a binary attractor neural network

International Nuclear Information System (INIS)

Koroutchev, Kostadin; Korutcheva, Elka

2006-01-01

The conditions for the formation of local bumps in the activity of binary attractor neural networks with spatially dependent connectivity are investigated. We show that these formations are observed when asymmetry between the activity during the retrieval and learning is imposed. An analytical approximation for the order parameters is derived. The corresponding phase diagram shows a relatively large and stable region where this effect is observed, although critical storage and information capacities drastically decrease inside that region. We demonstrate that the stability of the network, when starting from the bump formation, is larger than the stability when starting even from the whole pattern. Finally, we show a very good agreement between the analytical results and the simulations performed for different topologies of the network

Directed networks, allocation properties and hierarchy formation

NARCIS (Netherlands)

Slikker, M.; Gilles, R.P.; Norde, H.W.; Tijs, S.H.

2005-01-01

We investigate properties for allocation rules on directed communication networks and the formation of such networks under these payoff properties. We study allocation rules satisfying two appealing properties, Component Efficiency (CE) and the Hierarchical Payoff Property (HPP). We show that such

In vitro evaluation of carbon-nanotube-reinforced bioprintable vascular conduits

International Nuclear Information System (INIS)

Dolati, Farzaneh; Yu, Yin; Zhang, Yahui; Ozbolat, Ibrahim T; Jesus, Aribet M De; Sander, Edward A

2014-01-01

Vascularization of thick engineered tissue and organ constructs like the heart, liver, pancreas or kidney remains a major challenge in tissue engineering. Vascularization is needed to supply oxygen and nutrients and remove waste in living tissues and organs through a network that should possess high perfusion ability and significant mechanical strength and elasticity. In this paper, we introduce a fabrication process to print vascular conduits directly, where conduits were reinforced with carbon nanotubes (CNTs) to enhance their mechanical properties and bioprintability. In vitro evaluation of printed conduits encapsulated in human coronary artery smooth muscle cells was performed to characterize the effects of CNT reinforcement on the mechanical, perfusion and biological performance of the conduits. Perfusion and permeability, cell viability, extracellular matrix formation and tissue histology were assessed and discussed, and it was concluded that CNT-reinforced vascular conduits provided a foundation for mechanically appealing constructs where CNTs could be replaced with natural protein nanofibers for further integration of these conduits in large-scale tissue fabrication. (paper)

Influence of vascular network design on gas transfer in lung assist device technology.

Science.gov (United States)

Bassett, Erik K; Hoganson, David M; Lo, Justin H; Penson, Elliot J N; Vacanti, Joseph P

2011-01-01

Blood oxygenators are vital for the critically ill, but their use is limited to the hospital setting. A portable blood oxygenator or a lung assist device for ambulatory or long-term use would greatly benefit patients with chronic lung disease. In this work, a biomimetic blood oxygenator system was developed which consisted of a microfluidic vascular network covered by a gas permeable silicone membrane. This system was used to determine the influence of key microfluidic parameters-channel size, oxygen exposure length, and blood shear rate-on blood oxygenation and carbon dioxide removal. Total gas transfer increased linearly with flow rate, independent of channel size and oxygen exposure length. On average, CO(2) transfer was 4.3 times higher than oxygen transfer. Blood oxygen saturation was also found to depend on the flow rate per channel but in an inverse manner; oxygenation decreased and approached an asymptote as the flow rate per channel increased. These relationships can be used to optimize future biomimetic vascular networks for specific lung applications: gas transfer for carbon dioxide removal in patients with chronic obstructive pulmonary disease or oxygenation for premature infants requiring complete lung replacement therapy.

Social media in vascular surgery.

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Indes, Jeffrey E; Gates, Lindsay; Mitchell, Erica L; Muhs, Bart E

2013-04-01

There has been a tremendous growth in the use of social media to expand the visibility of various specialties in medicine. The purpose of this paper is to describe the latest updates on some current applications of social media in the practice of vascular surgery as well as existing limitations of use. This investigation demonstrates that the use of social networking sites appears to have a positive impact on vascular practice, as is evident through the incorporation of this technology at the Cleveland Clinic and by the Society for Vascular Surgery into their approach to patient care and physician communication. Overall, integration of social networking technology has current and future potential to be used to promote goals, patient awareness, recruitment for clinical trials, and professionalism within the specialty of vascular surgery. Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Radiotherapy in combination with vascular-targeted therapies

International Nuclear Information System (INIS)

Ciric, Eva; Sersa, Gregor

2010-01-01

Given the critical role of tumor vasculature in tumor development, considerable efforts have been spent on developing therapeutic strategies targeting the tumor vascular network. A variety of agents have been developed, with two general approaches being pursued. Antiangiogenic agents (AAs) aim to interfere with the process of angiogenesis, preventing new tumor blood vessel formation. Vascular-disrupting agents (VDAs) target existing tumor vessels causing tumor ischemia and necrosis. Despite their great therapeutic potential, it has become clear that their greatest clinical utility may lie in combination with conventional anticancer therapies. Radiotherapy is a widely used treatment modality for cancer with its distinct therapeutic challenges. Thus, combining the two approaches seems reasonable. Strong biological rationale exist for combining vascular-targeted therapies with radiation. AAs and VDAs were shown to alter the tumor microenvironment in such a way as to enhance responses to radiation. The results of preclinical and early clinical studies have confirmed the therapeutic potential of this new treatment strategy in the clinical setting. However, concerns about increased normal tissue toxicity, have been raised

Overlapping coalition formation games in wireless communication networks

CERN Document Server

Wang, Tianyu; Saad, Walid; Han, Zhu

2017-01-01

This brief introduces overlapping coalition formation games (OCF games), a novel mathematical framework from cooperative game theory that can be used to model, design and analyze cooperative scenarios in future wireless communication networks. The concepts of OCF games are explained, and several algorithmic aspects are studied. In addition, several major application scenarios are discussed. These applications are drawn from a variety of fields that include radio resource allocation in dense wireless networks, cooperative spectrum sensing for cognitive radio networks, and resource management for crowd sourcing. For each application, the use of OCF games is discussed in detail in order to show how this framework can be used to solve relevant wireless networking problems. Overlapping Coalition Formation Games in Wireless Communication Networks provides researchers, students and practitioners with a concise overview of existing works in this emerging area, exploring the relevant fundamental theories, key techniqu...

The construction of digital 3D arterial vascular network of uterine leiomyomas and its clinical significance

International Nuclear Information System (INIS)

Chen Chunlin; Xu Yujing; Liu Ping

2012-01-01

Objective: To discuss the method of constructing digital 3D arterial vascular network of uterine leiomyomas based on the CTA data, by which to lay the fundamental work for the observation of the origin and distribution of hysteromyoma blood supply. Methods: A total of 64 cases of uterine leiomyomas were enrolled in this study. Dual-source CT angiography was performed in all the patients, and the CTA original images were obtained. By using Mimics 10.01 software the digital 3D arterial vascular network of uterine was reconstructed. The reconstructed models were analyzed. Results: (1) The constructing process of arterial vascular network was successfully accomplished in all 64 patients. The pelvic main arteries, the uterine arteries and tumor-feeding arteries as well as the blood distribution type were clearly demonstrated on the reconstructed images. (2) The origins of hysteromyoma blood supply included uterine artery (81.25%), uterine artery and unilateral ovarian artery (10.94%), uterine artery and bilateral ovarian artery (4.69%) and ovarian artery (3.12%). (3) Distribution pattern of blood supply of uterine leiomyomas could be divided into 4 types: (1) Type Ⅰ. The unilateral arterial blood supply dominant type (unilateral uterine artery with or without ipsilateral ovarian arterial, providing more than 1/2 blood supply of hysteromyoma), which accounted for 35.94% of all patients (23/26); (2) Type Ⅱ. The bilateral arterial blood supply balanced type (bilateral uterine artery with or without ipsilateral ovarian artery, providing about 1/2 blood supply of hysteromyoma), which accounted for 53.13% of all patients (34/64); (3) Type Ⅲ. The unilateral uterine artery was the main blood supply of uterine leiomyomas, which accounted for 7.81% of all patients (5/64); (4) Type Ⅳ. The ovarian artery was the main blood supply of uterine leiomyomas, which accounted for 3.13% of all patients (3/64). Conclusion: Based on CTA data and with the help of reconstruction

Social network composition of vascular patients and its associations with health behavior and clinical risk factors

NARCIS (Netherlands)

Heijmans, N.; Lieshout, J. van; Wensing, M.

2017-01-01

BACKGROUND: This study aimed to explore linkages of patients' social network composition with health behaviors and clinical risk factors. METHODS/DESIGN: This observational study was embedded in a project aimed at improving cardiovascular risk management (CRVM) in primary care. 657 vascular patients

A meta-analysis of aneurysm formation in laser assisted vascular anastomosis (LAVA)

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Chen, Chen; Peng, Fei; Xu, Dahai; Cheng, Qinghua

2009-08-01

Laser assisted vascular anastomosis (LAVA) is looked as a particularly promising non-suture method in future. However, aneurysm formation is one of the main reasons delay the clinical application of LAVA. Some scientists investigated the incidence of aneurysms in animal model. To systematically analyze the literature on reported incidence of aneurysm formation in LAVA therapy, we performed a meta-analysis comparing LAVA with conventional suture anastomosis (CSA) in animal model. Data were systematically retrieved and selected from PUBMED. In total, 23 studies were retrieved. 18 studies were excluded, and 5 studies involving 647 animals were included. Analysis suggested no statistically significant difference between LAVA and CSA (OR 1.24, 95%CI 0.66-2.32, P=0.51). Result of meta analysis shows that the technology of LAVA is very close to clinical application.

Vasohibin inhibits angiogenic sprouting in vitro and supports vascular maturation processes in vivo

International Nuclear Information System (INIS)

Kern, Johann; Steurer, Michael; Gastl, Günther; Gunsilius, Eberhard; Untergasser, Gerold

2009-01-01

The murine homologue of human vasohibin (mVASH1), a putative antiangiogenic protein, was investigated for its effects on in vitro and in vivo angiogenesis. Cell growth and migration were analyzed in murine fibroblasts, smooth muscle cells and endothelial cells. Angiogenic sprouting was studied in human umbilical vein endothelial cells (HUVECs) in the spheroid sprouting assay. In vivo effects on blood vessel formation were investigated in the chorioallantoic membrane (CAM) assay and in the C57BL/6 melanoma xenograft model. Purified murine and human VASH1 protein induced apoptosis of murine fibroblasts in vitro, but not of vascular aortic smooth muscle cells (AoSMC) or endothelial cells. Adenoviral overexpression of murine and human VASH1 inhibited capillary sprouting of HUVECs in the spheroid assay. Administration of recombinant murine and human VASH1 inhibited growth of large vessels in the CAM assay and promoted the formation of a dense, fine vascular network. Murine VASH1-overexpressing B16F10 melanomas displayed a reduction in large vessels and vascular area. Moreover, tumors showed more microvessels that stained positive for the mural cell markers α-smooth muscle cell actin (ASMA) and proteoglycan (NG2). Our data imply that murine VASH1 causes angiogenic remodelling by inhibiting angiogenic sprouting and large vessel growth, thereby supporting the formation of a vascular bed consisting predominantly of mature microvessels

Retinal vascular segmentation using superpixel-based line operator and its application to vascular topology estimation.

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Na, Tong; Xie, Jianyang; Zhao, Yitian; Zhao, Yifan; Liu, Yue; Wang, Yongtian; Liu, Jiang

2018-05-09

Automatic methods of analyzing of retinal vascular networks, such as retinal blood vessel detection, vascular network topology estimation, and arteries/veins classification are of great assistance to the ophthalmologist in terms of diagnosis and treatment of a wide spectrum of diseases. We propose a new framework for precisely segmenting retinal vasculatures, constructing retinal vascular network topology, and separating the arteries and veins. A nonlocal total variation inspired Retinex model is employed to remove the image intensity inhomogeneities and relatively poor contrast. For better generalizability and segmentation performance, a superpixel-based line operator is proposed as to distinguish between lines and the edges, thus allowing more tolerance in the position of the respective contours. The concept of dominant sets clustering is adopted to estimate retinal vessel topology and classify the vessel network into arteries and veins. The proposed segmentation method yields competitive results on three public data sets (STARE, DRIVE, and IOSTAR), and it has superior performance when compared with unsupervised segmentation methods, with accuracy of 0.954, 0.957, and 0.964, respectively. The topology estimation approach has been applied to five public databases (DRIVE,STARE, INSPIRE, IOSTAR, and VICAVR) and achieved high accuracy of 0.830, 0.910, 0.915, 0.928, and 0.889, respectively. The accuracies of arteries/veins classification based on the estimated vascular topology on three public databases (INSPIRE, DRIVE and VICAVR) are 0.90.9, 0.910, and 0.907, respectively. The experimental results show that the proposed framework has effectively addressed crossover problem, a bottleneck issue in segmentation and vascular topology reconstruction. The vascular topology information significantly improves the accuracy on arteries/veins classification. © 2018 American Association of Physicists in Medicine.

Metabolic Vascular Syndrome: New Insights into a Multidimensional Network of Risk Factors and Diseases.

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Scholz, Gerhard H; Hanefeld, Markolf

2016-10-01

Since 1981, we have used the term metabolic syndrome to describe an association of a dysregulation in lipid metabolism (high triglycerides, low high-density lipoprotein cholesterol, disturbed glucose homeostasis (enhanced fasting and/or prandial glucose), gout, and hypertension), with android obesity being based on a common soil (overnutrition, reduced physical activity, sociocultural factors, and genetic predisposition). We hypothesized that main traits of the syndrome occur early and are tightly connected with hyperinsulinemia/insulin resistance, procoagulation, and cardiovascular diseases. To establish a close link between the traits of the metabolic vascular syndrome, we focused our literature search on recent original work and comprehensive reviews dealing with the topics metabolic syndrome, visceral obesity, fatty liver, fat tissue inflammation, insulin resistance, atherogenic dyslipidemia, arterial hypertension, and type 2 diabetes mellitus. Recent research supports the concept that the metabolic vascular syndrome is a multidimensional and interactive network of risk factors and diseases based on individual genetic susceptibility and epigenetic changes where metabolic dysregulation/metabolic inflexibility in different organs and vascular dysfunction are early interconnected. The metabolic vascular syndrome is not only a risk factor constellation but rather a life-long abnormality of a closely connected interactive cluster of developing diseases which escalate each other and should continuously attract the attention of every clinician.

Continuum Modeling of Biological Network Formation

KAUST Repository

Albi, Giacomo; Burger, Martin; Haskovec, Jan; Markowich, Peter A.; Schlottbom, Matthias

2017-01-01

We present an overview of recent analytical and numerical results for the elliptic–parabolic system of partial differential equations proposed by Hu and Cai, which models the formation of biological transportation networks. The model describes

Overexpression of Catalase in Vascular Smooth Muscle Cells Prevents the Formation of Abdominal Aortic Aneurysms

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Parastatidis, Ioannis; Weiss, Daiana; Joseph, Giji; Taylor, W Robert

2013-01-01

Objective Elevated levels of oxidative stress have been reported in abdominal aortic aneurysms (AAA), but which reactive oxygen species (ROS) promotes the development of AAA remains unclear. Here we investigate the effect of the hydrogen peroxide (H2O2) degrading enzyme catalase on the formation of AAA. Approach and Results AAA were induced with the application of calcium chloride (CaCl2) on mouse infrarenal aortas. The administration of PEG-catalase, but not saline, attenuated the loss of tunica media and protected against AAA formation (0.91±0.1 mm vs. 0.76±0.09 mm). Similarly, in a transgenic mouse model, catalase over-expression in the vascular smooth muscle cells (VSMC) preserved the thickness of tunica media and inhibited aortic dilatation by 50% (0.85±0.14 mm vs. 0.57±0.08 mm). Further studies showed that injury with CaCl2 decreased catalase expression and activity in the aortic wall. Pharmacologic administration or genetic over-expression of catalase restored catalase activity and subsequently decreased matrix metalloproteinase activity. In addition, a profound reduction in inflammatory markers and VSMC apoptosis was evident in aortas of catalase over-expressing mice. Interestingly, as opposed to infusion of PEG-catalase, chronic over-expression of catalase in VSMC did not alter the total aortic H2O2 levels. Conclusions The data suggest that a reduction in aortic wall catalase activity can predispose to AAA formation. Restoration of catalase activity in the vascular wall enhances aortic VSMC survival and prevents AAA formation primarily through modulation of matrix metalloproteinase activity. PMID:23950141

Injectable and inherently vascularizing semi-interpenetrating polymer network for delivering cells to the subcutaneous space.

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Mahou, Redouan; Zhang, David K Y; Vlahos, Alexander E; Sefton, Michael V

2017-07-01

Injectable hydrogels are suitable for local cell delivery to the subcutaneous space, but the lack of vasculature remains a limiting factor. Previously we demonstrated that biomaterials containing methacrylic acid promoted vascularization. Here we report the preparation of a semi-interpenetrating polymer network (SIPN), and its evaluation as an injectable carrier to deliver cells and generate blood vessels in a subcutaneous implantation site. The SIPN was prepared by reacting a blend of vinyl sulfone-terminated polyethylene glycol (PEG-VS) and sodium polymethacrylate (PMAA-Na) with dithiothreitol. The swelling of SIPN was sensitive to the PMAA-Na content but only small differences in gelation time, permeability and stiffness were noted. SIPN containing 20 mol% PMAA-Na generated a vascular network in the surrounding tissues, with 2-3 times as many vessels as was obtained with 10 mol% PMAA-Na or PEG alone. Perfusion studies showed that the generated vessels were perfused and connected to the host vasculature as early as seven days after transplantation. Islets embedded in SIPN were viable and responsive to glucose stimulation in vitro. In a proof of concept study in a streptozotocin-induced diabetic mouse model, a progressive return to normoglycemia was observed and the presence of insulin positive islets was confirmed when islets were embedded in SIPN prior to delivery. Our approach proposes a biomaterial-mediated strategy to deliver cells while enhancing vascularization. Copyright © 2017 Elsevier Ltd. All rights reserved.

Modulation of VEGF-induced migration and network formation by lymphatic endothelial cells: Roles of platelets and podoplanin.

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Langan, Stacey A; Navarro-Núñez, Leyre; Watson, Steve P; Nash, Gerard B

2017-07-20

Lymphatic endothelial cells (LEC) express the transmembrane receptor podoplanin whose only known endogenous ligand CLEC-2 is found on platelets. Both podoplanin and CLEC-2 are required for normal lymphangiogenesis as mice lacking either protein develop a blood-lymphatic mixing phenotype. We investigated the roles of podoplanin and its interaction with platelets in migration and tube formation by LEC. Addition of platelets or antibody-mediated crosslinking of podoplanin inhibited LEC migration induced by vascular endothelial growth factors (VEGF-A or VEGF-C), but did not modify basal migration or the response to basic fibroblast growth factor or epidermal growth factor. In addition, platelets and podoplanin crosslinking disrupted networks of LEC formed in co-culture with fibroblasts. Depletion of podoplanin in LEC using siRNA negated the pro-migratory effect of VEGF-A and VEGF-C. Inhibition of RhoA or Rho-kinase reduced LEC migration induced by VEGF-C, but had no further effect after crosslinking of podoplanin, suggesting that podoplanin is required for signaling downstream of VEGF-receptors but upstream of RhoA. Together, these data reveal for the first time that podoplanin is an intrinsic specific regulator of VEGF-mediated migration and network formation in LEC and identify crosslinking of podoplanin by platelets or antibodies as mechanisms to modulate this pathway.

Simulating the formation of keratin filament networks by a piecewise-deterministic Markov process.

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Beil, Michael; Lück, Sebastian; Fleischer, Frank; Portet, Stéphanie; Arendt, Wolfgang; Schmidt, Volker

2009-02-21

Keratin intermediate filament networks are part of the cytoskeleton in epithelial cells. They were found to regulate viscoelastic properties and motility of cancer cells. Due to unique biochemical properties of keratin polymers, the knowledge of the mechanisms controlling keratin network formation is incomplete. A combination of deterministic and stochastic modeling techniques can be a valuable source of information since they can describe known mechanisms of network evolution while reflecting the uncertainty with respect to a variety of molecular events. We applied the concept of piecewise-deterministic Markov processes to the modeling of keratin network formation with high spatiotemporal resolution. The deterministic component describes the diffusion-driven evolution of a pool of soluble keratin filament precursors fueling various network formation processes. Instants of network formation events are determined by a stochastic point process on the time axis. A probability distribution controlled by model parameters exercises control over the frequency of different mechanisms of network formation to be triggered. Locations of the network formation events are assigned dependent on the spatial distribution of the soluble pool of filament precursors. Based on this modeling approach, simulation studies revealed that the architecture of keratin networks mostly depends on the balance between filament elongation and branching processes. The spatial distribution of network mesh size, which strongly influences the mechanical characteristics of filament networks, is modulated by lateral annealing processes. This mechanism which is a specific feature of intermediate filament networks appears to be a major and fast regulator of cell mechanics.

Cardiovascular risk factors and collateral artery formation.

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de Groot, D; Pasterkamp, G; Hoefer, I E

2009-12-01

Arterial lumen narrowing and vascular occlusion is the actual cause of morbidity and mortality in atherosclerotic disease. Collateral artery formation (arteriogenesis) refers to an active remodelling of non-functional vascular anastomoses to functional collateral arteries, capable to bypass the site of obstruction and preserve the tissue that is jeopardized by ischaemia. Hemodynamic forces such as shear stress and wall stress play a pivotal role in collateral artery formation, accompanied by the expression of various cytokines and invasion of circulating leucocytes. Arteriogenesis hence represents an important compensatory mechanism for atherosclerotic vessel occlusion. As arteriogenesis mostly occurs when lumen narrowing by atherosclerotic plaques takes place, presence of cardiovascular risk factors (e.g. hypertension, hypercholesterolaemia and diabetes) is highly likely. Risk factors for atherosclerotic disease affect collateral artery growth directly and indirectly by altering hemodynamic forces or influencing cellular function and proliferation. Adequate collateralization varies significantly among atherosclerotic patients, some profit from the presence of extensive collateral networks, whereas others do not. Cardiovascular risk factors could increase the risk of adverse cardiovascular events in certain patients because of the reduced protection through an alternative vascular network. Likewise, drugs primarily thought to control cardiovascular risk factors might contribute or counteract collateral artery growth. This review summarizes current knowledge on the influence of cardiovascular risk factors and the effects of cardiovascular medication on the development of collateral vessels in experimental and clinical studies.

Biofabrication enables efficient interrogation and optimization of sequential culture of endothelial cells, fibroblasts and cardiomyocytes for formation of vascular cords in cardiac tissue engineering

International Nuclear Information System (INIS)

Iyer, Rohin K; Radisic, Milica; Chiu, Loraine L Y; Vunjak-Novakovic, Gordana

2012-01-01

We previously reported that preculture of fibroblasts (FBs) and endothelial cells (ECs) prior to cardiomyocytes (CMs) improved the structural and functional properties of engineered cardiac tissue compared to culture of CMs alone or co-culture of all three cell types. However, these approaches did not result in formation of capillary-like cords, which are precursors to vascularization in vivo. Here we hypothesized that seeding the ECs first on Matrigel and then FBs 24 h later to stabilize the endothelial network (sequential preculture) would enhance cord formation in engineered cardiac organoids. Three sequential preculture groups were tested by seeding ECs (D4T line) at 8%, 15% and 31% of the total cell number on Matrigel-coated microchannels and incubating for 24 h. Cardiac FBs were then seeded (32%, 25% and 9% of the total cell number, respectively) and incubated an additional 24 h. Finally, neonatal rat CMs (60% of the total cell number) were added and the organoids were cultivated for seven days. Within 24 h, the 8% EC group formed elongated cords which eventually developed into beating cylindrical organoids, while the 15% and 31% EC groups proliferated into flat EC monolayers with poor viability. Excitation threshold (ET) in the 8% EC group (3.4 ± 1.2 V cm −1 ) was comparable to that of the CM group (3.3 ± 1.4 V cm −1 ). The ET worsened with increasing EC seeding density (15% EC: 4.4 ± 1.5 V cm −1 ; 31% EC: 4.9 ± 1.5 V cm −1 ). Thus, sequential preculture promoted vascular cord formation and enhanced architecture and function of engineered heart tissues. (paper)

Cell sheet engineering using the stromal vascular fraction of adipose tissue as a vascularization strategy.

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Costa, Marina; Cerqueira, Mariana T; Santos, Tírcia C; Sampaio-Marques, Belém; Ludovico, Paula; Marques, Alexandra P; Pirraco, Rogério P; Reis, Rui L

2017-06-01

Current vascularization strategies for Tissue Engineering constructs, in particular cell sheet-based, are limited by time-consuming and expensive endothelial cell isolation and/or by the complexity of using extrinsic growth factors. Herein, we propose an alternative strategy using angiogenic cell sheets (CS) obtained from the stromal vascular fraction (SVF) of adipose tissue that can be incorporated into more complex constructs. Cells from the SVF were cultured in normoxic and hypoxic conditions for up to 8days in the absence of extrinsic growth factors. Immunocytochemistry against CD31 and CD146 revealed spontaneous organization in capillary-like structures, more complex after hypoxic conditioning. Inhibition of HIF-1α pathway hindered capillary-like structure formation in SVF cells cultured in hypoxia, suggesting a role of HIF-1α. Moreover, hypoxic SVF cells showed a trend for increased secretion of angiogenic factors, which was reflected in increased network formation by endothelial cells cultured on matrigel using that conditioned medium. In vivo implantation of SVF CS in a mouse hind limb ischemia model revealed that hypoxia-conditioned CS led to improved restoration of blood flow. Both in vitro and in vivo data suggest that SVF CS can be used as simple and cost-efficient tools to promote functional vascularization of TE constructs. Neovascularization after implantation is a major obstacle for producing clinically viable cell sheet-based tissue engineered constructs. Strategies using endothelial cells and extrinsic angiogenic growth factors are expensive and time consuming and may raise concerns of tumorigenicity. In this manuscript, we describe a simplified approach using angiogenic cell sheets fabricated from the stromal vascular fraction of adipose tissue. The strong angiogenic behavior of these cell sheets, achieved without the use of external growth factors, was further stimulated by low oxygen culture. When implanted in an in vivo model of hind limb

Opinion formation on multiplex scale-free networks

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Nguyen, Vu Xuan; Xiao, Gaoxi; Xu, Xin-Jian; Li, Guoqi; Wang, Zhen

2018-01-01

Most individuals, if not all, live in various social networks. The formation of opinion systems is an outcome of social interactions and information propagation occurring in such networks. We study the opinion formation with a new rule of pairwise interactions in the novel version of the well-known Deffuant model on multiplex networks composed of two layers, each of which is a scale-free network. It is found that in a duplex network composed of two identical layers, the presence of the multiplexity helps either diminish or enhance opinion diversity depending on the relative magnitudes of tolerance ranges characterizing the degree of openness/tolerance on both layers: there is a steady separation between different regions of tolerance range values on two network layers where multiplexity plays two different roles, respectively. Additionally, the two critical tolerance ranges follow a one-sum rule; that is, each of the layers reaches a complete consensus only if the sum of the tolerance ranges on the two layers is greater than a constant approximately equaling 1, the double of the critical bound on a corresponding isolated network. A further investigation of the coupling between constituent layers quantified by a link overlap parameter reveals that as the layers are loosely coupled, the two opinion systems co-evolve independently, but when the inter-layer coupling is sufficiently strong, a monotonic behavior is observed: an increase in the tolerance range of a layer causes a decline in the opinion diversity on the other layer regardless of the magnitudes of tolerance ranges associated with the layers in question.

Integration of hormonal signaling networks and mobile microRNAs is required for vascular patterning in Arabidopsis roots

KAUST Repository

Muraro, D.

2013-12-31

As multicellular organisms grow, positional information is continually needed to regulate the pattern in which cells are arranged. In the Arabidopsis root, most cell types are organized in a radially symmetric pattern; however, a symmetry-breaking event generates bisymmetric auxin and cytokinin signaling domains in the stele. Bidirectional cross-talk between the stele and the surrounding tissues involving a mobile transcription factor, SHORT ROOT (SHR), and mobile microRNA species also determines vascular pattern, but it is currently unclear how these signals integrate. We use a multicellular model to determine a minimal set of components necessary for maintaining a stable vascular pattern. Simulations perturbing the signaling network show that, in addition to the mutually inhibitory interaction between auxin and cytokinin, signaling through SHR, microRNA165/6, and PHABULOSA is required to maintain a stable bisymmetric pattern. We have verified this prediction by observing loss of bisymmetry in shr mutants. The model reveals the importance of several features of the network, namely the mutual degradation of microRNA165/6 and PHABULOSA and the existence of an additional negative regulator of cytokinin signaling. These components form a plausible mechanism capable of patterning vascular tissues in the absence of positional inputs provided by the transport of hormones from the shoot.

Integration of hormonal signaling networks and mobile microRNAs is required for vascular patterning in Arabidopsis roots

KAUST Repository

Muraro, D.; Mellor, N.; Pound, M. P.; Help, H.; Lucas, M.; Chopard, J.; Byrne, H. M.; Godin, C.; Hodgman, T. C.; King, J. R.; Pridmore, T. P.; Helariutta, Y.; Bennett, M. J.; Bishopp, A.

2013-01-01

As multicellular organisms grow, positional information is continually needed to regulate the pattern in which cells are arranged. In the Arabidopsis root, most cell types are organized in a radially symmetric pattern; however, a symmetry-breaking event generates bisymmetric auxin and cytokinin signaling domains in the stele. Bidirectional cross-talk between the stele and the surrounding tissues involving a mobile transcription factor, SHORT ROOT (SHR), and mobile microRNA species also determines vascular pattern, but it is currently unclear how these signals integrate. We use a multicellular model to determine a minimal set of components necessary for maintaining a stable vascular pattern. Simulations perturbing the signaling network show that, in addition to the mutually inhibitory interaction between auxin and cytokinin, signaling through SHR, microRNA165/6, and PHABULOSA is required to maintain a stable bisymmetric pattern. We have verified this prediction by observing loss of bisymmetry in shr mutants. The model reveals the importance of several features of the network, namely the mutual degradation of microRNA165/6 and PHABULOSA and the existence of an additional negative regulator of cytokinin signaling. These components form a plausible mechanism capable of patterning vascular tissues in the absence of positional inputs provided by the transport of hormones from the shoot.

A natural experiment of social network formation and dynamics.

Science.gov (United States)

Phan, Tuan Q; Airoldi, Edoardo M

2015-05-26

Social networks affect many aspects of life, including the spread of diseases, the diffusion of information, the workers' productivity, and consumers' behavior. Little is known, however, about how these networks form and change. Estimating causal effects and mechanisms that drive social network formation and dynamics is challenging because of the complexity of engineering social relations in a controlled environment, endogeneity between network structure and individual characteristics, and the lack of time-resolved data about individuals' behavior. We leverage data from a sample of 1.5 million college students on Facebook, who wrote more than 630 million messages and 590 million posts over 4 years, to design a long-term natural experiment of friendship formation and social dynamics in the aftermath of a natural disaster. The analysis shows that affected individuals are more likely to strengthen interactions, while maintaining the same number of friends as unaffected individuals. Our findings suggest that the formation of social relationships may serve as a coping mechanism to deal with high-stress situations and build resilience in communities.

Dynamics of Research Team Formation in Complex Networks

Science.gov (United States)

Sun, Caihong; Wan, Yuzi; Chen, Yu

Most organizations encourage the formation of teams to accomplish complicated tasks, and vice verse, effective teams could bring lots benefits and profits for organizations. Network structure plays an important role in forming teams. In this paper, we specifically study the dynamics of team formation in large research communities in which knowledge of individuals plays an important role on team performance and individual utility. An agent-based model is proposed, in which heterogeneous agents from research communities are described and empirically tested. Each agent has a knowledge endowment and a preference for both income and leisure. Agents provide a variable input (‘effort’) and their knowledge endowments to production. They could learn from others in their team and those who are not in their team but have private connections in community to adjust their own knowledge endowment. They are allowed to join other teams or work alone when it is welfare maximizing to do so. Various simulation experiments are conducted to examine the impacts of network topology, knowledge diffusion among community network, and team output sharing mechanisms on the dynamics of team formation.

Dll4-Notch signaling determines the formation of native arterial collateral networks and arterial function in mouse ischemia models.

Science.gov (United States)

Cristofaro, Brunella; Shi, Yu; Faria, Marcella; Suchting, Steven; Leroyer, Aurelie S; Trindade, Alexandre; Duarte, Antonio; Zovein, Ann C; Iruela-Arispe, M Luisa; Nih, Lina R; Kubis, Nathalie; Henrion, Daniel; Loufrani, Laurent; Todiras, Mihail; Schleifenbaum, Johanna; Gollasch, Maik; Zhuang, Zhen W; Simons, Michael; Eichmann, Anne; le Noble, Ferdinand

2013-04-01

Arteriogenesis requires growth of pre-existing arteriolar collateral networks and determines clinical outcome in arterial occlusive diseases. Factors responsible for the development of arteriolar collateral networks are poorly understood. The Notch ligand Delta-like 4 (Dll4) promotes arterial differentiation and restricts vessel branching. We hypothesized that Dll4 may act as a genetic determinant of collateral arterial networks and functional recovery in stroke and hind limb ischemia models in mice. Genetic loss- and gain-of-function approaches in mice showed that Dll4-Notch signaling restricts pial collateral artery formation by modulating arterial branching morphogenesis during embryogenesis. Adult Dll4(+/-) mice showed increased pial collateral numbers, but stroke volume upon middle cerebral artery occlusion was not reduced compared with wild-type littermates. Likewise, Dll4(+/-) mice showed reduced blood flow conductance after femoral artery occlusion, and, despite markedly increased angiogenesis, tissue ischemia was more severe. In peripheral arteries, loss of Dll4 adversely affected excitation-contraction coupling in arterial smooth muscle in response to vasopressor agents and arterial vessel wall adaption in response to increases in blood flow, collectively contributing to reduced flow reserve. We conclude that Dll4-Notch signaling modulates native collateral formation by acting on vascular branching morphogenesis during embryogenesis. Dll4 furthermore affects tissue perfusion by acting on arterial function and structure. Loss of Dll4 stimulates collateral formation and angiogenesis, but in the context of ischemic diseases such beneficial effects are overruled by adverse functional changes, demonstrating that ischemic recovery is not solely determined by collateral number but rather by vessel functionality.

Dll4-Notch signaling determines the formation of native arterial collateral networks and arterial function in mouse ischemia models

Science.gov (United States)

Cristofaro, Brunella; Shi, Yu; Faria, Marcella; Suchting, Steven; Leroyer, Aurelie S.; Trindade, Alexandre; Duarte, Antonio; Zovein, Ann C.; Iruela-Arispe, M. Luisa; Nih, Lina R.; Kubis, Nathalie; Henrion, Daniel; Loufrani, Laurent; Todiras, Mihail; Schleifenbaum, Johanna; Gollasch, Maik; Zhuang, Zhen W.; Simons, Michael; Eichmann, Anne; le Noble, Ferdinand

2013-01-01

Arteriogenesis requires growth of pre-existing arteriolar collateral networks and determines clinical outcome in arterial occlusive diseases. Factors responsible for the development of arteriolar collateral networks are poorly understood. The Notch ligand Delta-like 4 (Dll4) promotes arterial differentiation and restricts vessel branching. We hypothesized that Dll4 may act as a genetic determinant of collateral arterial networks and functional recovery in stroke and hind limb ischemia models in mice. Genetic loss- and gain-of-function approaches in mice showed that Dll4-Notch signaling restricts pial collateral artery formation by modulating arterial branching morphogenesis during embryogenesis. Adult Dll4+/- mice showed increased pial collateral numbers, but stroke volume upon middle cerebral artery occlusion was not reduced compared with wild-type littermates. Likewise, Dll4+/- mice showed reduced blood flow conductance after femoral artery occlusion, and, despite markedly increased angiogenesis, tissue ischemia was more severe. In peripheral arteries, loss of Dll4 adversely affected excitation-contraction coupling in arterial smooth muscle in response to vasopressor agents and arterial vessel wall adaption in response to increases in blood flow, collectively contributing to reduced flow reserve. We conclude that Dll4-Notch signaling modulates native collateral formation by acting on vascular branching morphogenesis during embryogenesis. Dll4 furthermore affects tissue perfusion by acting on arterial function and structure. Loss of Dll4 stimulates collateral formation and angiogenesis, but in the context of ischemic diseases such beneficial effects are overruled by adverse functional changes, demonstrating that ischemic recovery is not solely determined by collateral number but rather by vessel functionality. PMID:23533173

Network formation under heterogeneous costs: The multiple group model

NARCIS (Netherlands)

Kamphorst, J.J.A.; van der Laan, G.

2007-01-01

It is widely recognized that the shape of networks influences both individual and aggregate behavior. This raises the question which types of networks are likely to arise. In this paper we investigate a model of network formation, where players are divided into groups and the costs of a link between

Dynamic adaption of vascular morphology

DEFF Research Database (Denmark)

Okkels, Fridolin; Jacobsen, Jens Christian Brings

2012-01-01

The structure of vascular networks adapts continuously to meet changes in demand of the surrounding tissue. Most of the known vascular adaptation mechanisms are based on local reactions to local stimuli such as pressure and flow, which in turn reflects influence from the surrounding tissue. Here ...

Magnolol inhibits migration of vascular smooth muscle cells via cytoskeletal remodeling pathway to attenuate neointima formation

International Nuclear Information System (INIS)

Karki, Rajendra; Kim, Seong-Bin; Kim, Dong-Wook

2013-01-01

Background: Increased proliferation and migration of vascular smooth muscle cells (VSMCs) contribute importantly to the formation of both atherosclerotic and restenotic lesions. The objective of this study was to investigate the effect of magnolol on VSMC migration. Methods: The proteolytic activity of matrix metalloproteinases (MMPs) in tumor necrosis factor alpha (TNF-α) stimulated VSMCs was performed by gelatin zymography. VSMC migration was assessed by wound healing and Boyden chamber methods. Collagen induced VSMC adhesion was determined by spectrofluorimeter and stress fibers formation was evaluated by fluorescence microscope. The expression of signaling molecules involved in stress fibers formation was determined by western blot. The phosphorylation of myosin light chain (MLC20) was determined by urea-glycerol polyacrylamide gel electrophoresis. Immunohistochemistry was performed to determine the expression of β1-integrin and collagen type I in the injured carotid arteries of rats on day 35 after vascular injury. Results: VSMC migration was strongly inhibited by magnolol without affecting MMPs expression. Also, magnolol inhibited β1-integrin expression, FAK phosphorylation and RhoA and Cdc42 activation to inhibit the collagen induced stress fibers formation. Moreover, magnolol inhibited the phosphorylation of MLC20. Our in vivo results showed that magnolol inhibited β1-integrin expression, collagen type I deposition and FAK phosphorylation in injured carotid arteries without affecting MMP-2 activity. Conclusions: Magnolol inhibited VSMC migration via inhibition of cytoskeletal remodeling pathway to attenuate neointima formation. General significance: This study provides a rationale for further evaluation of magnolol for the management of atherosclerosis and restenosis. - Highlights: • Magnolol strongly inhibited migration of VSMCs. • Magnolol inhibited stress fibers formation. • MLC20 phosphorylation was also inhibited by magnolol. • Anti

Magnolol inhibits migration of vascular smooth muscle cells via cytoskeletal remodeling pathway to attenuate neointima formation

Energy Technology Data Exchange (ETDEWEB)

Karki, Rajendra [Division of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City (United States); Department of Oriental Medicine Resources, Mokpo National University (Korea, Republic of); Kim, Seong-Bin [Jeollanamdo Development Institute for Korean Traditional Medicine, Jangheung gun, Jeollanamdo (Korea, Republic of); Kim, Dong-Wook, E-mail: dbkim@mokpo.ac.kr [Department of Oriental Medicine Resources, Mokpo National University (Korea, Republic of)

2013-12-10

Background: Increased proliferation and migration of vascular smooth muscle cells (VSMCs) contribute importantly to the formation of both atherosclerotic and restenotic lesions. The objective of this study was to investigate the effect of magnolol on VSMC migration. Methods: The proteolytic activity of matrix metalloproteinases (MMPs) in tumor necrosis factor alpha (TNF-α) stimulated VSMCs was performed by gelatin zymography. VSMC migration was assessed by wound healing and Boyden chamber methods. Collagen induced VSMC adhesion was determined by spectrofluorimeter and stress fibers formation was evaluated by fluorescence microscope. The expression of signaling molecules involved in stress fibers formation was determined by western blot. The phosphorylation of myosin light chain (MLC20) was determined by urea-glycerol polyacrylamide gel electrophoresis. Immunohistochemistry was performed to determine the expression of β1-integrin and collagen type I in the injured carotid arteries of rats on day 35 after vascular injury. Results: VSMC migration was strongly inhibited by magnolol without affecting MMPs expression. Also, magnolol inhibited β1-integrin expression, FAK phosphorylation and RhoA and Cdc42 activation to inhibit the collagen induced stress fibers formation. Moreover, magnolol inhibited the phosphorylation of MLC20. Our in vivo results showed that magnolol inhibited β1-integrin expression, collagen type I deposition and FAK phosphorylation in injured carotid arteries without affecting MMP-2 activity. Conclusions: Magnolol inhibited VSMC migration via inhibition of cytoskeletal remodeling pathway to attenuate neointima formation. General significance: This study provides a rationale for further evaluation of magnolol for the management of atherosclerosis and restenosis. - Highlights: • Magnolol strongly inhibited migration of VSMCs. • Magnolol inhibited stress fibers formation. • MLC20 phosphorylation was also inhibited by magnolol. • Anti

Vascular function in health, hypertension, and diabetes

DEFF Research Database (Denmark)

Nyberg, Michael Permin; Gliemann, Lasse; Hellsten, Ylva

2015-01-01

muscle, which can affect muscle function. Central aspects in the vascular impairments are alterations in the formation of prostacyclin, the bioavailability of NO and an increased formation of vasoconstrictors and reactive oxygen species (ROS). Regular physical activity effectively improves vascular......, the increase in muscle blood flow required for oxygen supply during exercise is achieved through a substantial increase in vasodilators locally formed in the active muscle tissue that overcome the vasoconstrictor signals. Most of the vasodilator signals are mediated via endothelial cells, which lead...... to the formation of vasodilators such as nitric oxide (NO) and prostacyclin. In essential hypertension and type II diabetes, the endothelial function and regulation of vascular tone is impaired with consequent increases in peripheral vascular resistance and inadequate regulation of oxygen supply to the skeletal...

Improved vascularization of planar membrane diffusion devices following continuous infusion of vascular endothelial growth factor.

Science.gov (United States)

Trivedi, N; Steil, G M; Colton, C K; Bonner-Weir, S; Weir, G C

2000-01-01

Improving blood vessel formation around an immunobarrier device should improve the survival of the encapsulated tissue. In the present study we investigated the formation of new blood vessels around a planar membrane diffusion device (the Baxter Theracyte System) undergoing a continuous infusion of vascular endothelial growth factor through the membranes and into the surrounding tissue. Each device (20 microl) had both an inner immunoisolation membrane and an outer vascularizing membrane. Human recombinant vascular endothelial growth factor-165 was infused at 100 ng/day (low dose: n = 6) and 500 ng/day (high dose: n = 7) for 10 days into devices implanted s.c. in Sprague-Dawley rats; noninfused devices transplanted for an identical period were used as controls (n = 5). Two days following the termination of VEGF infusion, devices were loaded with 20 microl of Lispro insulin (1 U/kg) and the kinetics of insulin release from the lumen of the device was assessed. Devices were then explanted and the number of blood vessels (capillary and noncapillary) was quantified using morphometry. High-dose vascular endothelial growth factor infusion resulted in two- to threefold more blood vessels around the device than that obtained with the noninfused devices and devices infused with low-dose vascular endothelial growth factor. This increase in the number of blood vessels was accompanied by a modest increase in insulin diffusion from the device in the high-dose vascular endothelial growth factor infusion group. We conclude that vascular endothelial growth factor can be used to improve blood vessel formation adjacent to planar membrane diffusion devices.

Mathematical Analysis of a PDE System for Biological Network Formation

KAUST Repository

Haskovec, Jan

2015-02-04

Motivated by recent physics papers describing rules for natural network formation, we study an elliptic-parabolic system of partial differential equations proposed by Hu and Cai [13, 15]. The model describes the pressure field thanks to Darcy\\'s type equation and the dynamics of the conductance network under pressure force effects with a diffusion rate D >= 0 representing randomness in the material structure. We prove the existence of global weak solutions and of local mild solutions and study their long term behavior. It turns out that, by energy dissipation, steady states play a central role to understand the network formation capacity of the system. We show that for a large diffusion coefficient D, the zero steady state is stable, while network formation occurs for small values of D due to the instability of the zero steady state, and the borderline case D = 0 exhibits a large class of dynamically stable (in the linearized sense) steady states.

Master stability functions reveal diffusion-driven pattern formation in networks

Science.gov (United States)

Brechtel, Andreas; Gramlich, Philipp; Ritterskamp, Daniel; Drossel, Barbara; Gross, Thilo

2018-03-01

We study diffusion-driven pattern formation in networks of networks, a class of multilayer systems, where different layers have the same topology, but different internal dynamics. Agents are assumed to disperse within a layer by undergoing random walks, while they can be created or destroyed by reactions between or within a layer. We show that the stability of homogeneous steady states can be analyzed with a master stability function approach that reveals a deep analogy between pattern formation in networks and pattern formation in continuous space. For illustration, we consider a generalized model of ecological meta-food webs. This fairly complex model describes the dispersal of many different species across a region consisting of a network of individual habitats while subject to realistic, nonlinear predator-prey interactions. In this example, the method reveals the intricate dependence of the dynamics on the spatial structure. The ability of the proposed approach to deal with this fairly complex system highlights it as a promising tool for ecology and other applications.

Phenotypic modulation of smooth muscle cells during formation of neointimal thickenings following vascular injury.

Science.gov (United States)

Thyberg, J

1998-07-01

Smooth muscle cells build up the media of mammalian arteries and constitute one of the principal cell types in atherosclerotic and restenotic lesions. Accordingly, they show a high degree of plasticity and are able to shift from a differentiated, contractile phenotype to a less differentiated, synthetic phenotype, and then back again. This modulation occurs as a response to vascular injury and includes a prominent structural reorganization with loss of myofilaments and formation of an extensive endoplasmic reticulum and a large Golgi complex. At the same time, the expression of cytoskeletal proteins and other gene products is altered. As a result, the cells lose their contractility and become able to migrate from the media to the intima, proliferate, and secrete extracellular matrix components, thereby contributing to the formation of intimal thickenings. The mechanisms behind this change in morphology and function of the smooth muscle cells are still incompletely understood. A crucial role has been ascribed to basement membrane proteins such as laminin and collagen type IV and adhesive proteins such as fibronectin. A significant role is also played by mitogenic proteins such as platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF). An improved knowledge of the regulation of smooth muscle differentiated properties represents an important part in the search for new methods of prevention and treatment of vascular disease.

Vascular tissue engineering by computer-aided laser micromachining.

Science.gov (United States)

Doraiswamy, Anand; Narayan, Roger J

2010-04-28

Many conventional technologies for fabricating tissue engineering scaffolds are not suitable for fabricating scaffolds with patient-specific attributes. For example, many conventional technologies for fabricating tissue engineering scaffolds do not provide control over overall scaffold geometry or over cell position within the scaffold. In this study, the use of computer-aided laser micromachining to create scaffolds for vascular tissue networks was investigated. Computer-aided laser micromachining was used to construct patterned surfaces in agarose or in silicon, which were used for differential adherence and growth of cells into vascular tissue networks. Concentric three-ring structures were fabricated on agarose hydrogel substrates, in which the inner ring contained human aortic endothelial cells, the middle ring contained HA587 human elastin and the outer ring contained human aortic vascular smooth muscle cells. Basement membrane matrix containing vascular endothelial growth factor and heparin was to promote proliferation of human aortic endothelial cells within the vascular tissue networks. Computer-aided laser micromachining provides a unique approach to fabricate small-diameter blood vessels for bypass surgery as well as other artificial tissues with complex geometries.

Umbilical Cord Blood-Derived Mononuclear Cells Exhibit Pericyte-Like Phenotype and Support Network Formation of Endothelial Progenitor Cells In Vitro.

Science.gov (United States)

Peters, Erica B; Liu, Betty; Christoforou, Nicolas; West, Jennifer L; Truskey, George A

2015-10-01

Umbilical cord blood represents a promising cell source for pro-angiogenic therapies. The present study examined the potential of mononuclear cells (MNCs) from umbilical cord blood to support endothelial progenitor cell (EPC) microvessel formation. MNCs were isolated from the cord blood of 20 separate donors and selected for further characterization based upon their proliferation potential and morphological resemblance to human vascular pericytes (HVPs). MNCs were screened for their ability to support EPC network formation using an in vitro assay (Matrigel™) as well as a reductionist, coculture system consisting of no additional angiogenic cytokines beyond those present in serum. In less than 15% of the isolations, we identified a population of highly proliferative MNCs that phenotypically resembled HVPs as assessed by expression of PDGFR-β, NG2, α-SMA, and ephrin-B2. Within a Matrigel™ system, MNCs demonstrated pericyte-like function through colocalization to EPC networks and similar effects as HVPs upon total EPC tubule length (p = 0.95) and number of branch points (p = 0.93). In a reductionist coculture system, MNCs served as pro-angiogenic mural cells by supporting EPC network formation to a significantly greater extent than HVP cocultures, by day 14 of coculture, as evidenced through EPC total tubule length (p < 0.0001) and number of branch points (p < 0.0001). Our findings are significant as we demonstrate mural cell progenitors can be isolated from umbilical cord blood and develop culture conditions to support their use in microvascular tissue engineering applications.

STEREOLOGICAL ANALYSIS OF THE HUMAN PONS VASCULAR NETWORK

Directory of Open Access Journals (Sweden)

Ivan Jovanović

2003-04-01

Full Text Available Liver is the largest parenchymatous organ, well vascularized, weighing approximately 1.8-3.0% of the whole body weight. Among all abdominal traumas liver injuries account for 25%. For more serious liver injuries the mortality is around 40% in children below 10 years of age. For lesions of the juxtahepatic veins (three major hepatic veins or the retrohepatic portion of v. cava or for complex, combined intra abdominal injuries, the mortality is even up to 70%.This work analyzed the period 1988-2000 during which there were 19 children admitted and treated for blunt liver injuries at the Clinic of Pediatric Surgery and Orthopedics in Nis; I, II and III scale injuries prevailed (17 cases; 89.4%. These injuries were surgically treated for the most part (17 cases; 89.4%. In 7 children (36.8% there were combined injuries. The lethality was 26.3%-5 cases, with three major complications: two intrahepatic hematomas and one biliary fistula associated with biliary peritonitis and biloma formation.

Social power and opinion formation in complex networks

Science.gov (United States)

Jalili, Mahdi

2013-02-01

In this paper we investigate the effects of social power on the evolution of opinions in model networks as well as in a number of real social networks. A continuous opinion formation model is considered and the analysis is performed through numerical simulation. Social power is given to a proportion of agents selected either randomly or based on their degrees. As artificial network structures, we consider scale-free networks constructed through preferential attachment and Watts-Strogatz networks. Numerical simulations show that scale-free networks with degree-based social power on the hub nodes have an optimal case where the largest number of the nodes reaches a consensus. However, given power to a random selection of nodes could not improve consensus properties. Introducing social power in Watts-Strogatz networks could not significantly change the consensus profile.

Hydrogels with precisely controlled integrin activation dictate vascular patterning and permeability

Science.gov (United States)

Li, Shuoran; Nih, Lina R.; Bachman, Haylee; Fei, Peng; Li, Yilei; Nam, Eunwoo; Dimatteo, Robert; Carmichael, S. Thomas; Barker, Thomas H.; Segura, Tatiana

2017-09-01

Integrin binding to bioengineered hydrogel scaffolds is essential for tissue regrowth and regeneration, yet not all integrin binding can lead to tissue repair. Here, we show that through engineering hydrogel materials to promote α3/α5β1 integrin binding, we can promote the formation of a space-filling and mature vasculature compared with hydrogel materials that promote αvβ3 integrin binding. In vitro, α3/α5β1 scaffolds promoted endothelial cells to sprout and branch, forming organized extensive networks that eventually reached and anastomosed with neighbouring branches. In vivo, α3/α5β1 scaffolds delivering vascular endothelial growth factor (VEGF) promoted non-tortuous blood vessel formation and non-leaky blood vessels by 10 days post-stroke. In contrast, materials that promote αvβ3 integrin binding promoted endothelial sprout clumping in vitro and leaky vessels in vivo. This work shows that precisely controlled integrin activation from a biomaterial can be harnessed to direct therapeutic vessel regeneration and reduce VEGF-induced vascular permeability in vivo.

Epigenetic regulation of vascular smooth muscle cell proliferation and neointima formation by histone deacetylase inhibition.

Science.gov (United States)

Findeisen, Hannes M; Gizard, Florence; Zhao, Yue; Qing, Hua; Heywood, Elizabeth B; Jones, Karrie L; Cohn, Dianne; Bruemmer, Dennis

2011-04-01

Proliferation of smooth muscle cells (SMC) in response to vascular injury is central to neointimal vascular remodeling. There is accumulating evidence that histone acetylation constitutes a major epigenetic modification for the transcriptional control of proliferative gene expression; however, the physiological role of histone acetylation for proliferative vascular disease remains elusive. In the present study, we investigated the role of histone deacetylase (HDAC) inhibition in SMC proliferation and neointimal remodeling. We demonstrate that mitogens induce transcription of HDAC 1, 2, and 3 in SMC. Short interfering RNA-mediated knockdown of either HDAC 1, 2, or 3 and pharmacological inhibition of HDAC prevented mitogen-induced SMC proliferation. The mechanisms underlying this reduction of SMC proliferation by HDAC inhibition involve a growth arrest in the G(1) phase of the cell cycle that is due to an inhibition of retinoblastoma protein phosphorylation. HDAC inhibition resulted in a transcriptional and posttranscriptional regulation of the cyclin-dependent kinase inhibitors p21(Cip1) and p27(Kip). Furthermore, HDAC inhibition repressed mitogen-induced cyclin D1 mRNA expression and cyclin D1 promoter activity. As a result of this differential cell cycle-regulatory gene expression by HDAC inhibition, the retinoblastoma protein retains a transcriptional repression of its downstream target genes required for S phase entry. Finally, we provide evidence that these observations are applicable in vivo by demonstrating that HDAC inhibition decreased neointima formation and expression of cyclin D1 in a murine model of vascular injury. These findings identify HDAC as a critical component of a transcriptional cascade regulating SMC proliferation and suggest that HDAC might play a pivotal role in the development of proliferative vascular diseases, including atherosclerosis and in-stent restenosis.

Vascular ring complicates accidental button battery ingestion.

Science.gov (United States)

Mercer, Ronald W; Schwartz, Matthew C; Stephany, Joshua; Donnelly, Lane F; Franciosi, James P; Epelman, Monica

2015-01-01

Button battery ingestion can lead to dangerous complications, including vasculoesophageal fistula formation. The presence of a vascular ring may complicate battery ingestion if the battery lodges at the level of the ring and its important vascular structures. We report a 4-year-old boy with trisomy 21 who was diagnosed with a vascular ring at the time of button battery ingestion and died 9 days after presentation due to massive upper gastrointestinal bleeding from esophageal erosion and vasculoesophageal fistula formation. Copyright © 2015 Elsevier Inc. All rights reserved.

Formation of actin networks in microfluidic concentration gradients

Directory of Open Access Journals (Sweden)

Natalja eStrelnikova

2016-05-01

Full Text Available The physical properties of cytoskeletal networks are contributors in a number of mechanical responses of cells including cellular deformation and locomotion, and are crucial for the proper action of living cells. Local chemical gradients modulate cytoskeletal functionality including the interactions of the cytoskeleton with other cellular components. Actin is a major constituent of the cytoskeleton. Introducing a microfluidic-based platform, we explored the impact of concentration gradients on the formation and structural properties of actin networks. Microfluidics-controlled flow-free steady state experimental conditions allow for the generation of chemical gradients of different profiles, such as linear or step-like. We discovered specific features of actin networks emerging in defined gradients. In particular, we analyzed the effects of spatial conditions on network properties, bending rigidities of network links, and the network elasticity.

Time course of fibronectin in the peri-implant tissue and neointima formation after functional implantation of polyester-based vascular prostheses with different porosity in pigs

Energy Technology Data Exchange (ETDEWEB)

Patrzyk, Maciej; Hoene, Andreas [Department of Surgery, Ernst Moritz Arndt University Greifswald, Friedrich-Loeffler-Str. 23, D-17489 Greifswald (Germany); Jarchow, Raymond [Computation Centre, Ernst Moritz Arndt University Greifswald, Felix-Hausdorff-Str. 12, D-17489 Greifswald (Germany); Wilhelm, Lutz [Department of Surgery, Hospital Demmin, Loitzer Str. 1, D-17109 Demmin (Germany); Walschus, Uwe; Schlosser, Michael [Research Group of Predictive Diagnostics of the Department of Medical Biochemistry and Molecular Biology and Institute of Pathophysiology, Ernst Moritz Arndt University Greifswald, Greifswalder Str. 11c, D-17495 Karlsburg (Germany); Zippel, Roland, E-mail: schlosse@uni-greifswald.d [Department of Surgery, Elbland Hospital Center, Weinbergstr. 8, D-01589 Riesa (Germany)

2010-10-01

Intima hyperplasia, resulting from extracellular matrix (ECM) secretion, can lead to vascular prosthesis occlusion and is a major problem in vascular surgery. Fibronectin might contribute to ongoing ECM secretion. However, the exact role of fibronectin and its influence on neointima formation remains unclear. This study was aimed at investigating the time course of the fibronectin area fraction and neointima formation following the functional implantation of three different polyester vascular prostheses into pigs. The infrarenal aorta from 15 animals (n = 5/group) was replaced by prosthesis segments with low, medium and high primary porosity. After 7, 14, 21, 28 and 116 days, the prostheses were morphometrically examined. Overall, the fibronectin area fraction was inversely correlated with the neointima thickness, demonstrating high fibronectin levels in the early phase (days 7 and 14) and low levels in the later phase with almost complete neointima formation (days 21-116). Throughout the study, fibronectin levels were highest at the proximal anastomosis region. The low porosity prosthesis had the highest fibronectin area fraction and a delayed neointima formation in the middle phase (days 21 and 28) but the highest neointima lining on day 116. The results indicate a relationship between fibronectin and neointima formation with the prosthesis porosity, demonstrating the importance of the textile design for tissue reactions following implantation.

Genetic Regulation of Vascular Development: Building the Zebrafish Vascular Tree

NARCIS (Netherlands)

R.L.J.M. Herpers (Robert)

2010-01-01

textabstractThe extensive networks of blood and lymphatic vessels within the vertebrate body are essential for the transport and delivery of fluids, gases, macromolecules and cells, and play important roles in facilitating immune responses. The development of the vascular tree requires a highly

Opinion formation driven by PageRank node influence on directed networks

Science.gov (United States)

Eom, Young-Ho; Shepelyansky, Dima L.

2015-10-01

We study a two states opinion formation model driven by PageRank node influence and report an extensive numerical study on how PageRank affects collective opinion formations in large-scale empirical directed networks. In our model the opinion of a node can be updated by the sum of its neighbor nodes' opinions weighted by the node influence of the neighbor nodes at each step. We consider PageRank probability and its sublinear power as node influence measures and investigate evolution of opinion under various conditions. First, we observe that all networks reach steady state opinion after a certain relaxation time. This time scale is decreasing with the heterogeneity of node influence in the networks. Second, we find that our model shows consensus and non-consensus behavior in steady state depending on types of networks: Web graph, citation network of physics articles, and LiveJournal social network show non-consensus behavior while Wikipedia article network shows consensus behavior. Third, we find that a more heterogeneous influence distribution leads to a more uniform opinion state in the cases of Web graph, Wikipedia, and Livejournal. However, the opposite behavior is observed in the citation network. Finally we identify that a small number of influential nodes can impose their own opinion on significant fraction of other nodes in all considered networks. Our study shows that the effects of heterogeneity of node influence on opinion formation can be significant and suggests further investigations on the interplay between node influence and collective opinion in networks.

3D printed scaffolds of calcium silicate-doped β-TCP synergize with co-cultured endothelial and stromal cells to promote vascularization and bone formation.

Science.gov (United States)

Deng, Yuan; Jiang, Chuan; Li, Cuidi; Li, Tao; Peng, Mingzheng; Wang, Jinwu; Dai, Kerong

2017-07-17

Synthetic bone scaffolds have potential application in repairing large bone defects, however, inefficient vascularization after implantation remains the major issue of graft failure. Herein, porous β-tricalcium phosphate (β-TCP) scaffolds with calcium silicate (CS) were 3D printed, and pre-seeded with co-cultured human umbilical cord vein endothelial cells (HUVECs) and human bone marrow stromal cells (hBMSCs) to construct tissue engineering scaffolds with accelerated vascularization and better bone formation. Results showed that in vitro β-TCP scaffolds doped with 5% CS (5%CS/β-TCP) were biocompatible, and stimulated angiogenesis and osteogenesis. The results also showed that 5%CS/β-TCP scaffolds not only stimulated co-cultured cells angiogenesis on Matrigel, but also stimulated co-cultured cells to form microcapillary-like structures on scaffolds, and promoted migration of BMSCs by stimulating co-cultured cells to secrete PDGF-BB and CXCL12 into the surrounding environment. Moreover, 5%CS/β-TCP scaffolds enhanced vascularization and osteoinduction in comparison with β-TCP, and synergized with co-cultured cells to further increase early vessel formation, which was accompanied by earlier and better ectopic bone formation when implanted subcutaneously in nude mice. Thus, our findings suggest that porous 5%CS/β-TCP scaffolds seeded with co-cultured cells provide new strategy for accelerating tissue engineering scaffolds vascularization and osteogenesis, and show potential as treatment for large bone defects.

Continuum Modeling of Biological Network Formation

KAUST Repository

Albi, Giacomo

2017-04-10

We present an overview of recent analytical and numerical results for the elliptic–parabolic system of partial differential equations proposed by Hu and Cai, which models the formation of biological transportation networks. The model describes the pressure field using a Darcy type equation and the dynamics of the conductance network under pressure force effects. Randomness in the material structure is represented by a linear diffusion term and conductance relaxation by an algebraic decay term. We first introduce micro- and mesoscopic models and show how they are connected to the macroscopic PDE system. Then, we provide an overview of analytical results for the PDE model, focusing mainly on the existence of weak and mild solutions and analysis of the steady states. The analytical part is complemented by extensive numerical simulations. We propose a discretization based on finite elements and study the qualitative properties of network structures for various parameter values.

Matrix Metalloproteinases: Inflammatory Regulators of Cell Behaviors in Vascular Formation and Remodeling

Directory of Open Access Journals (Sweden)

Qishan Chen

2013-01-01

Full Text Available Abnormal angiogenesis and vascular remodeling contribute to pathogenesis of a number of disorders such as tumor, arthritis, atherosclerosis, restenosis, hypertension, and neurodegeneration. During angiogenesis and vascular remodeling, behaviors of stem/progenitor cells, endothelial cells (ECs, and vascular smooth muscle cells (VSMCs and its interaction with extracellular matrix (ECM play a critical role in the processes. Matrix metalloproteinases (MMPs, well-known inflammatory mediators are a family of zinc-dependent proteolytic enzymes that degrade various components of ECM and non-ECM molecules mediating tissue remodeling in both physiological and pathological processes. MMPs including MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-12, and MT1-MMP, are stimulated and activated by various stimuli in vascular tissues. Once activated, MMPs degrade ECM proteins or other related signal molecules to promote recruitment of stem/progenitor cells and facilitate migration and invasion of ECs and VSMCs. Moreover, vascular cell proliferation and apoptosis can also be regulated by MMPs via proteolytically cleaving and modulating bioactive molecules and relevant signaling pathways. Regarding the importance of vascular cells in abnormal angiogenesis and vascular remodeling, regulation of vascular cell behaviors through modulating expression and activation of MMPs shows therapeutic potential.

Omentopexy improves vascularization and decreases stricture formation of esophageal anastomoses in a dog model.

Science.gov (United States)

Hayari, Lili; Hershko, Dan D; Shoshani, Hadas; Maor, Ron; Mordecovich, Daniel; Shoshani, Gideon

2004-04-01

Anastomotic strictures are common after primary esophageal anastomosis in pediatric patients. Recent studies provided evidence that omentopexy may improve vascularization of gastroesophageal anastomoses and decrease the rate of stricture-related complications. The effect of omentopexy on primary esophago-esophageal anastomosis, however, is unknown. The aim of the current study was to examine the role of omentopexy on the healing process of primary midesopageal anastomoses. Six dogs were operated on. A 5-cm portion of the midesophagus was resected, and continuity was restored by end-to-end anastomosis. In 3 dogs, an omental pedicle was placed around the anastomotic region. Eating patterns were recorded and functional swallowing was evaluated by fluoroscopic studies. Eight weeks after the operations, the experimental animals were killed and anastomotic lumen diameters and vascularization of the anastomotic sites were evaluated by radiographic studies and histologic examination, respectively. Two dogs in the omentopexy group were able to resume regular feeding, whereas none of the dogs in the control group were able to tolerate solid food intake. Fluoroscopic studies found preserved motility patterns of the esophagus in the omentoesophagopexy group, while prestenotic dilatation and delayed food clearance through the anastomosis were observed in the control group. Histologically, neovascularization was observed at the anastomotic site in the omentoesophagopexy group in contrast to the marked degree of fibrosis displayed in the control group. Omentopexy may improve vascularization and decrease stricture formation after primary esophagoesophageal anastomosis.

The formation of a core-periphery structure in heterogeneous financial networks

NARCIS (Netherlands)

van der Leij, M.; in 't Veld, D.; Hommes, C.

2016-01-01

Recent empirical evidence suggests that financial networks exhibit a core-periphery network structure. This paper aims at giving an explanation for the emergence of such a structure using network formation theory. We propose a simple model of the overnight interbank lending market, in which banks

Identification of cyst nematode B-type CLE peptides and modulation of the vascular stem cell pathway for feeding cell formation

Science.gov (United States)

Stem cells are important in the continuous formation of various tissues during postembryonic organogenesis. Stem cell pools in the SAM (shoot apical meristem), RAM (root apical meristem) and vascular procambium/cambium are regulated by CLE-receptor kinase-WOX signaling modules. Previous data showed ...

Advanced Modulation Formats in Cognitive Optical Networks: EU project CHRON Demonstration

DEFF Research Database (Denmark)

Borkowski, Robert; Caballero Jambrina, Antonio; Klonidis, Dimitris

2014-01-01

We demonstrate real-time path establishment and switching of coherent modulation formats (QPSK, 16QAM) within an optical network driven by cognitive algorithms. Cognition aims at autonomous configuration optimization to satisfy quality of transmission requirements.......We demonstrate real-time path establishment and switching of coherent modulation formats (QPSK, 16QAM) within an optical network driven by cognitive algorithms. Cognition aims at autonomous configuration optimization to satisfy quality of transmission requirements....

Vascular risk factors, cerebrovascular reactivity, and the default-mode brain network.

Science.gov (United States)

Haight, Thaddeus J; Bryan, R Nick; Erus, Guray; Davatzikos, Christos; Jacobs, David R; D'Esposito, Mark; Lewis, Cora E; Launer, Lenore J

2015-07-15

Cumulating evidence from epidemiologic studies implicates cardiovascular health and cerebrovascular function in several brain diseases in late life. We examined vascular risk factors with respect to a cerebrovascular measure of brain functioning in subjects in mid-life, which could represent a marker of brain changes in later life. Breath-hold functional MRI (fMRI) was performed in 541 women and men (mean age 50.4 years) from the Coronary Artery Risk Development in Young Adults (CARDIA) Brain MRI sub-study. Cerebrovascular reactivity (CVR) was quantified as percentage change in blood-oxygen level dependent (BOLD) signal in activated voxels, which was mapped to a common brain template and log-transformed. Mean CVR was calculated for anatomic regions underlying the default-mode network (DMN) - a network implicated in AD and other brain disorders - in addition to areas considered to be relatively spared in the disease (e.g. occipital lobe), which were utilized as reference regions. Mean CVR was significantly reduced in the posterior cingulate/precuneus (β=-0.063, 95% CI: -0.106, -0.020), anterior cingulate (β=-0.055, 95% CI: -0.101, -0.010), and medial frontal lobe (β=-0.050, 95% CI: -0.092, -0.008) relative to mean CVR in the occipital lobe, after adjustment for age, sex, race, education, and smoking status, in subjects with pre-hypertension/hypertension compared to normotensive subjects. By contrast, mean CVR was lower, but not significantly, in the inferior parietal lobe (β=-0.024, 95% CI: -0.062, 0.014) and the hippocampus (β=-0.006, 95% CI: -0.062, 0.050) relative to mean CVR in the occipital lobe. Similar results were observed in subjects with diabetes and dyslipidemia compared to those without these conditions, though the differences were non-significant. Reduced CVR may represent diminished vascular functionality for the DMN for individuals with prehypertension/hypertension in mid-life, and may serve as a preclinical marker for brain dysfunction in later

Optical coherence tomography angiography indicates associations of the retinal vascular network and disease activity in multiple sclerosis.

Science.gov (United States)

Feucht, Nikolaus; Maier, Mathias; Lepennetier, Gildas; Pettenkofer, Moritz; Wetzlmair, Carmen; Daltrozzo, Tanja; Scherm, Pauline; Zimmer, Claus; Hoshi, Muna-Miriam; Hemmer, Bernhard; Korn, Thomas; Knier, Benjamin

2018-01-01

Patients with multiple sclerosis (MS) and clinically isolated syndrome (CIS) may show alterations of retinal layer architecture as measured by optical coherence tomography. Little is known about changes in the retinal vascular network during MS. To characterize retinal vessel structures in patients with MS and CIS and to test for associations with MS disease activity. In all, 42 patients with MS or CIS and 50 healthy controls underwent retinal optical coherence tomography angiography (OCT-A) with analysis of the superficial and deep vascular plexuses and the choriocapillaries. We tested OCT-A parameters for associations with retinal layer volumes, history of optic neuritis (ON), and the retrospective disease activity. Inner retinal layer volumes correlated positively with the density of both the superficial and deep vascular plexuses. Eyes of MS/CIS patients with a history of ON revealed reduced vessel densities of the superficial and deep vascular plexuses as compared to healthy controls. Higher choriocapillary vessel densities were associated with ongoing inflammatory disease activity during 24 months prior to OCT-A examination in MS and CIS patients. Optic neuritis is associated with rarefaction of the superficial and deep retinal vessels. Alterations of the choriocapillaries might be linked to disease activity in MS.

Neonatal brain hemorrhage (NBH) of prematurity: translational mechanisms of the vascular-neural network.

Science.gov (United States)

Lekic, Tim; Klebe, Damon; Poblete, Roy; Krafft, Paul R; Rolland, William B; Tang, Jiping; Zhang, John H

2015-01-01

Neonatal brain hemorrhage (NBH) of prematurity is an unfortunate consequence of preterm birth. Complications result in shunt dependence and long-term structural changes such as posthemorrhagic hydrocephalus, periventricular leukomalacia, gliosis, and neurological dysfunction. Several animal models are available to study this condition, and many basic mechanisms, etiological factors, and outcome consequences, are becoming understood. NBH is an important clinical condition, of which treatment may potentially circumvent shunt complication, and improve functional recovery (cerebral palsy, and cognitive impairments). This review highlights key pathophysiological findings of the neonatal vascular-neural network in the context of molecular mechanisms targeting the posthemorrhagic hydrocephalus affecting this vulnerable infant population.

Neonatal Brain Hemorrhage (NBH) of Prematurity: Translational Mechanisms of the Vascular-Neural Network

Science.gov (United States)

Lekic, Tim; Klebe, Damon; Poblete, Roy; Krafft, Paul R.; Rolland, William B.; Tang, Jiping; Zhang, John H.

2015-01-01

Neonatal brain hemorrhage (NBH) of prematurity is an unfortunate consequence of preterm birth. Complications result in shunt dependence and long-term structural changes such as post-hemorrhagic hydrocephalus, periventricular leukomalacia, gliosis, and neurological dysfunction. Several animal models are available to study this condition, and many basic mechanisms, etiological factors, and outcome consequences, are becoming understood. NBH is an important clinical condition, of which treatment may potentially circumvent shunt complication, and improve functional recovery (cerebral palsy, and cognitive impairments). This review highlights key pathophysiological findings of the neonatal vascular-neural network in the context of molecular mechanisms targeting the post-hemorrhagic hydrocephalus affecting this vulnerable infant population. PMID:25620100

PDZK1 prevents neointima formation via suppression of breakpoint cluster region kinase in vascular smooth muscle.

Directory of Open Access Journals (Sweden)

Wan Ru Lee

Full Text Available Scavenger receptor class B, type I (SR-BI and its adaptor protein PDZK1 mediate responses to HDL cholesterol in endothelium. Whether the receptor-adaptor protein tandem serves functions in other vascular cell types is unknown. The current work determined the roles of SR-BI and PDZK1 in vascular smooth muscle (VSM. To evaluate possible VSM functions of SR-BI and PDZK1 in vivo, neointima formation was assessed 21 days post-ligation in the carotid arteries of wild-type, SR-BI-/- or PDZK1-/- mice. Whereas neointima development was negligible in wild-type and SR-BI-/-, there was marked neointima formation in PDZK1-/- mice. PDZK1 expression was demonstrated in primary mouse VSM cells, and compared to wild-type cells, PDZK1-/- VSM displayed exaggerated proliferation and migration in response to platelet derived growth factor (PDGF. Tandem affinity purification-mass spectrometry revealed that PDZK1 interacts with breakpoint cluster region kinase (Bcr, which contains a C-terminal PDZ binding sequence and is known to enhance responses to PDGF in VSM. PDZK1 interaction with Bcr in VSM was demonstrated by pull-down and by coimmunoprecipitation, and the augmented proliferative response to PDGF in PDZK1-/- VSM was abrogated by Bcr depletion. Furthermore, compared with wild-type Bcr overexpression, the introduction of a Bcr mutant incapable of PDZK1 binding into VSM cells yielded an exaggerated proliferative response to PDGF. Thus, PDZK1 has novel SR-BI-independent function in VSM that affords protection from neointima formation, and this involves PDZK1 suppression of VSM cell proliferation via an inhibitory interaction with Bcr.

Self-healing sandwich structures incorporating an interfacial layer with vascular network

International Nuclear Information System (INIS)

Chen, Chunlin; Peters, Kara; Li, Yulong

2013-01-01

A self-healing capability specifically targeted for sandwich composite laminates based on interfacial layers with built-in vascular networks is presented. The self-healing occurs at the facesheet–core interface through an additional interfacial layer to seal facesheet cracks and rebond facesheet–core regions. The efficacy of introducing the self-healing system at the facesheet–core interface is evaluated through four-point bend and edgewise compression testing of representative foam core sandwich composite specimens with impact induced damage. The self-healing interfacial layer partially restored the specific initial stiffness, doubling the residual initial stiffness as compared to the control specimen after the impact event. The restoration of the ultimate specific skin strength was less successful. The results also highlight the critical challenge in self-healing of sandwich composites, which is to rebond facesheets which have separated from the core material. (paper)

Optimal Formation of Multirobot Systems Based on a Recurrent Neural Network.

Science.gov (United States)

Wang, Yunpeng; Cheng, Long; Hou, Zeng-Guang; Yu, Junzhi; Tan, Min

2016-02-01

The optimal formation problem of multirobot systems is solved by a recurrent neural network in this paper. The desired formation is described by the shape theory. This theory can generate a set of feasible formations that share the same relative relation among robots. An optimal formation means that finding one formation from the feasible formation set, which has the minimum distance to the initial formation of the multirobot system. Then, the formation problem is transformed into an optimization problem. In addition, the orientation, scale, and admissible range of the formation can also be considered as the constraints in the optimization problem. Furthermore, if all robots are identical, their positions in the system are exchangeable. Then, each robot does not necessarily move to one specific position in the formation. In this case, the optimal formation problem becomes a combinational optimization problem, whose optimal solution is very hard to obtain. Inspired by the penalty method, this combinational optimization problem can be approximately transformed into a convex optimization problem. Due to the involvement of the Euclidean norm in the distance, the objective function of these optimization problems are nonsmooth. To solve these nonsmooth optimization problems efficiently, a recurrent neural network approach is employed, owing to its parallel computation ability. Finally, some simulations and experiments are given to validate the effectiveness and efficiency of the proposed optimal formation approach.

MFAP4 Promotes Vascular Smooth Muscle Migration, Proliferation and Accelerates Neointima Formation

DEFF Research Database (Denmark)

Schlosser, Anders; Pilecki, Bartosz; Hemstra, Line E.

2016-01-01

in the vascular wall. The role of MFAP4 in vascular biology is unknown. We aimed to test the hypothesis that MFAP4 would enhance integrin-dependent VSMC activation. APPROACH AND RESULTS: We produced Mfap4-deficient (Mfap4(-/-)) mice and performed carotid artery ligation to explore the role of MFAP4 in vascular...... kinase and downstream kinases. In addition, we showed that MFAP4 promotes monocyte chemotaxis in integrin αVβ3-dependent manner. CONCLUSIONS: MFAP4 regulates integrin αVβ3-induced VSMC proliferation and migration, as well as monocyte chemotaxis, and accelerates neointimal hyperplasia after vascular...

Mean-field approach to evolving spatial networks, with an application to osteocyte network formation

Science.gov (United States)

Taylor-King, Jake P.; Basanta, David; Chapman, S. Jonathan; Porter, Mason A.

2017-07-01

We consider evolving networks in which each node can have various associated properties (a state) in addition to those that arise from network structure. For example, each node can have a spatial location and a velocity, or it can have some more abstract internal property that describes something like a social trait. Edges between nodes are created and destroyed, and new nodes enter the system. We introduce a "local state degree distribution" (LSDD) as the degree distribution at a particular point in state space. We then make a mean-field assumption and thereby derive an integro-partial differential equation that is satisfied by the LSDD. We perform numerical experiments and find good agreement between solutions of the integro-differential equation and the LSDD from stochastic simulations of the full model. To illustrate our theory, we apply it to a simple model for osteocyte network formation within bones, with a view to understanding changes that may take place during cancer. Our results suggest that increased rates of differentiation lead to higher densities of osteocytes, but with a smaller number of dendrites. To help provide biological context, we also include an introduction to osteocytes, the formation of osteocyte networks, and the role of osteocytes in bone metastasis.

FORMATION OF THE ICT COMPETENCE OF MANAGERIAL AND PEDAGOGICAL STAFF IN A NETWORKING

Directory of Open Access Journals (Sweden)

O. A. Kozlov

2016-01-01

Full Text Available The questions related to the preparation of modern pedagogical and managerial staff to implement the capabilities of information and communication technologies in the professional activities in terms of networking. The authors found that the scientific-pedagogical conditions of formation of the ICT competencies of management and teaching staff as the coordinator of modernization of education are: to form approaches and principles of formation of the ICT competencies of management and teaching staff and the willingness of the professional community in the formation of the ICT competencies of management and teaching staff as the modernization of the coordinators education in networking Determined ways and means to achieve teaching and administrative staff of professional ICT competence under network interaction. Said factors that provide an optimal model to achieve the professional pedagogical ICT competence and managerial personnel under network interaction.

Convergent evolution of vascular optimization in kelp (Laminariales).

Science.gov (United States)

Drobnitch, Sarah Tepler; Jensen, Kaare H; Prentice, Paige; Pittermann, Jarmila

2015-10-07

Terrestrial plants and mammals, although separated by a great evolutionary distance, have each arrived at a highly conserved body plan in which universal allometric scaling relationships govern the anatomy of vascular networks and key functional metabolic traits. The universality of allometric scaling suggests that these phyla have each evolved an 'optimal' transport strategy that has been overwhelmingly adopted by extant species. To truly evaluate the dominance and universality of vascular optimization, however, it is critical to examine other, lesser-known, vascularized phyla. The brown algae (Phaeophyceae) are one such group--as distantly related to plants as mammals, they have convergently evolved a plant-like body plan and a specialized phloem-like transport network. To evaluate possible scaling and optimization in the kelp vascular system, we developed a model of optimized transport anatomy and tested it with measurements of the giant kelp, Macrocystis pyrifera, which is among the largest and most successful of macroalgae. We also evaluated three classical allometric relationships pertaining to plant vascular tissues with a diverse sampling of kelp species. Macrocystis pyrifera displays strong scaling relationships between all tested vascular parameters and agrees with our model; other species within the Laminariales display weak or inconsistent vascular allometries. The lack of universal scaling in the kelps and the presence of optimized transport anatomy in M. pyrifera raises important questions about the evolution of optimization and the possible competitive advantage conferred by optimized vascular systems to multicellular phyla. © 2015 The Author(s).

Matrix protein of vesicular stomatitis virus: a potent inhibitor of vascular endothelial growth factor and malignant ascites formation.

Science.gov (United States)

Zhou, Y; Wen, F; Zhang, P; Tang, R; Li, Q

2013-03-01

Malignant ascites is common in various types of cancers and is difficult to manage. Vascular endothelial growth factor (VEGF) has a pivotal role in malignant ascites. The matrix protein of vesicular stomatitis virus (VSVMP) has been shown to inhibit host gene expression and induce the apoptosis of cancer cells. The present study was designed to determine whether VSVMP suppresses the formation of ascites in ascites-producing peritoneal carcinomatosis. BALB/c female mice, 6-8 weeks old, bearing peritoneal tumors of H22 or MethA cells received an intraperitoneal administration of 50 μg VSVMP/250 μg liposome complexes, 50 μg empty plasmid/250 μg liposome complexes or 0.9% NaCl solution, respectively, every 2 days for 3 weeks. Administration of VSVMP resulted in a significant inhibition in ascites formation, improvement in health condition and prolonged survival of the treated mice. Decreased peritoneum osmolarity and reduced tumor vascularity coincided with dramatic reductions in the VEGF level in ascites fluid and plasma. Examination of floating tumor cells collected from the peritoneal wash revealed an apparently increased number of apoptotic cells and profound downregulation of VEGF mRNA in the VSVMP-treated mice. Our data indicate for the first time that in BALB/c mice bearing H22 or MethA cell peritoneal tumors, VSVMP may inhibit VEGF production and suppress angiogenesis, consequently abolishing ascites formation.

3D-Printed Biodegradable Polymeric Vascular Grafts.

Science.gov (United States)

Melchiorri, A J; Hibino, N; Best, C A; Yi, T; Lee, Y U; Kraynak, C A; Kimerer, L K; Krieger, A; Kim, P; Breuer, C K; Fisher, J P

2016-02-04

Congenital heart defect interventions may benefit from the fabrication of patient-specific vascular grafts because of the wide array of anatomies present in children with cardiovascular defects. 3D printing is used to establish a platform for the production of custom vascular grafts, which are biodegradable, mechanically compatible with vascular tissues, and support neotissue formation and growth. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Unexpected role of the copper transporter ATP7A in PDGF-induced vascular smooth

Energy Technology Data Exchange (ETDEWEB)

Ashino, T.; Varadarajan, S.; Urao, N.; Oshikawa, J.; Chen, G. -F.; Wang, H.; Huo, Y.; Finney, L.; Vogt, S.; McKinney, R. D.; Maryon, E. B.; Kaplan, J. H.; Ushio-Fukai, M.; Fukai, T. (Biosciences Division); ( XSD); ( PSC-USR); (Univ. of Illinois at Chicago); (Univ. of Minnesota)

2010-09-09

Copper, an essential nutrient, has been implicated in vascular remodeling and atherosclerosis with unknown mechanism. Bioavailability of intracellular copper is regulated not only by the copper importer CTR1 (copper transporter 1) but also by the copper exporter ATP7A (Menkes ATPase), whose function is achieved through copper-dependent translocation from trans-Golgi network (TGN). Platelet-derived growth factor (PDGF) promotes vascular smooth muscle cell (VSMC) migration, a key component of neointimal formation. To determine the role of copper transporter ATP7A in PDGF-induced VSMC migration. Depletion of ATP7A inhibited VSMC migration in response to PDGF or wound scratch in a CTR1/copper-dependent manner. PDGF stimulation promoted ATP7A translocation from the TGN to lipid rafts, which localized at the leading edge, where it colocalized with PDGF receptor and Rac1, in migrating VSMCs. Mechanistically, ATP7A small interfering RNA or CTR small interfering RNA prevented PDGF-induced Rac1 translocation to the leading edge, thereby inhibiting lamellipodia formation. In addition, ATP7A depletion prevented a PDGF-induced decrease in copper level and secretory copper enzyme precursor prolysyl oxidase (Pro-LOX) in lipid raft fraction, as well as PDGF-induced increase in LOX activity. In vivo, ATP7A expression was markedly increased and copper accumulation was observed by synchrotron-based x-ray fluorescence microscopy at neointimal VSMCs in wire injury model. These findings suggest that ATP7A plays an important role in copper-dependent PDGF-stimulated VSMC migration via recruiting Rac1 to lipid rafts at the leading edge, as well as regulating LOX activity. This may contribute to neointimal formation after vascular injury. Our findings provide insight into ATP7A as a novel therapeutic target for vascular remodeling and atherosclerosis.

Convergent evolution of vascular optimization in kelp (Laminariales)

DEFF Research Database (Denmark)

Drobnitch, Sarah Tepler; Jensen, Kaare Hartvig; Prentice, Paige

2015-01-01

Terrestrial plants and mammals, although separated by a great evolutionary distance, have each arrived at a highly conserved body plan in which universal allometric scaling relationships govern the anatomy of vascular networks and key functional metabolic traits. The universality of allometric...... (Phaeophyceae) are one such group—as distantly related to plants as mammals, they have convergently evolved a plant-like body plan and a specialized phloem-like transport network. To evaluate possible scaling and optimization in the kelp vascular system, we developed a model of optimized transport anatomy...... and tested it with measurements of the giant kelp, Macrocystis pyrifera, which is among the largest and most successful of macroalgae. We also evaluated three classical allometric relationships pertaining to plant vascular tissues with a diverse sampling of kelp species. Macrocystis pyrifera displays strong...

Vascular Nitric Oxide-Superoxide Balance and Thrombus Formation after Acute Exercise.

Science.gov (United States)

Przyborowski, Kamil; Proniewski, Bartosz; Czarny, Joanna; Smeda, Marta; Sitek, Barbara; Zakrzewska, Agnieszka; Zoladz, Jerzy A; Chlopicki, Stefan

2018-02-21

An acute bout of strenuous exercise in humans results in transient impairment of NO-dependent function, but it remains unknown whether this phenomenon is associated with increased risk of post-exercise thrombotic events. This study aimed to evaluate effects of a single bout of exhaustive running in mice on the balance of vascular nitric oxide (NO)/reactive oxygen species (ROS) production, and on thrombogenicity. At different time-points (0h, 2h and 4h) after exercise and in sedentary C57BL/6 mice the production of NO and superoxide (O2) in aorta was measured by electron paramagnetic resonance (EPR) spin trapping and by dihydroethidium (DHE)/HPLC-based method, respectively, while collagen-induced thrombus formation was analyzed in a microchip-based flow-chamber system (T-TAS). We also measured pre- and post-exercise plasma concentration of nitrite/nitrate and 6-keto-PGF1α. An acute bout of exhaustive running in mice resulted in decreased production of NO and increased production of O2 in aorta, with maximum changes 2h after completion of exercise when compared to sedentary mice. However, platelet thrombus formation was not changed by exercise as evidenced by unaltered time to start of thrombus formation (T10) and capillary occlusion (OT), and total thrombogenicity (AUC) as measured in a flow-chamber system. Strenuous exercise increased the plasma concentration of nitrite but did not affect nitrate and 6-keto-PGF1α concentrations. An acute bout of strenuous exercise in mice reduced NO and in parallel increased O2 production in aorta. This response was most pronounced 2h after exercise. Surprisingly, the reduced NO and increased O2 production did not result in increased post-exercise platelet-dependent thrombogenicity. These results show that transient reduction in NO bioavailability, caused by exercise-induced oxidative stress, does not modify post-exercise thromboresistance in healthy mice.

Vascular malforma- tions part 1 — normal and abnormal vascular ...

African Journals Online (AJOL)

Enrique

to form the primitive vascular plexus. Angiogenesis is the formation of new vessels by sprouting or splitting of ... The differentiation of primitive vessels into arteries, veins or capillaries is determined by flow patterns .... identify, but it is probable that as time progresses further specific genetic defects related to the development ...

In vivo endothelization of tubular vascular grafts through in situ recruitment of endothelial and endothelial progenitor cells by RGD-fused mussel adhesive proteins

International Nuclear Information System (INIS)

Kang, Tae-Yun; Lee, Jung Ho; Kang, Jo-A; Rhie, Jong-Won; Kim, Bum Jin; Cha, Hyung Joon; Hong, Jung Min; Kim, Byoung Soo; Cho, Dong-Woo

2015-01-01

The use of tissue mimics in vivo, including patterned vascular networks, is expected to facilitate the regeneration of functional tissues and organs with large volumes. Maintaining patency of channels in contact with blood is an important issue in the development of a functional vascular network. Endothelium is the only known completely non-thrombogenic material; however, results from treatments to induce endothelialization are inconclusive. The present study was designed to evaluate the clinical applicability of in situ recruitment of endothelial cells/endothelial progenitor cells (EC/EPC) and pre-endothelization using a recombinant mussel adhesive protein fused with arginine–glycine–aspartic acid peptide (MAP-RGD) coating in a model of vascular graft implantation. Microporous polycaprolactone (PCL) scaffolds were fabricated with salt leaching methods and their surfaces were modified with collagen and MAP-RGD. We then evaluated their anti-thrombogenicity with an in vitro hemocompatibility assessment and a 4-week implantation in the rabbit carotid artery. We observed that MAP-RGD coating reduced the possibility of early in vivo graft failure and enhanced re-endothelization by in situ recruitment of EC/EPC (patency rate: 2/3), while endothelization prior to implantation aggravated the formation of thrombosis and/or IH (patency rate: 0/3). The results demonstrated that in situ recruitment of EC/EPC by MAP-RGD could be a promising strategy for vascular applications. In addition, it rules out several issues associated with pre-endothelization, such as cell source, purity, functional modulation and contamination. Further evaluation of long term performance and angiogenesis from the luminal surface may lead to the clinical use of MAP-RGD for tubular vascular grafts and regeneration of large-volume tissues with functional vascular networks. (paper)

System level mechanisms of adaptation, learning, memory formation and evolvability: the role of chaperone and other networks.

Science.gov (United States)

Gyurko, David M; Soti, Csaba; Stetak, Attila; Csermely, Peter

2014-05-01

During the last decade, network approaches became a powerful tool to describe protein structure and dynamics. Here, we describe first the protein structure networks of molecular chaperones, then characterize chaperone containing sub-networks of interactomes called as chaperone-networks or chaperomes. We review the role of molecular chaperones in short-term adaptation of cellular networks in response to stress, and in long-term adaptation discussing their putative functions in the regulation of evolvability. We provide a general overview of possible network mechanisms of adaptation, learning and memory formation. We propose that changes of network rigidity play a key role in learning and memory formation processes. Flexible network topology provides ' learning-competent' state. Here, networks may have much less modular boundaries than locally rigid, highly modular networks, where the learnt information has already been consolidated in a memory formation process. Since modular boundaries are efficient filters of information, in the 'learning-competent' state information filtering may be much smaller, than after memory formation. This mechanism restricts high information transfer to the 'learning competent' state. After memory formation, modular boundary-induced segregation and information filtering protect the stored information. The flexible networks of young organisms are generally in a 'learning competent' state. On the contrary, locally rigid networks of old organisms have lost their 'learning competent' state, but store and protect their learnt information efficiently. We anticipate that the above mechanism may operate at the level of both protein-protein interaction and neuronal networks.

Digital Identity Formation: Socially Being Real and Present on Digital Networks

Science.gov (United States)

Bozkurt, Aras; Tu, Chih-Hsiung

2016-01-01

Social networks have become popular communication and interaction environments recently. As digital environments, so as ecosystems, they have potential in terms of networked learning as they fulfill some roles such as mediating an environment for digital identity formation and providing social and emotional presence. Based on this phenomenon, the…

Neuronal sFlt1 and Vegfaa determine venous sprouting and spinal cord vascularization

DEFF Research Database (Denmark)

Wild, Raphael; Klems, Alina; Takamiya, Masanari

2017-01-01

Formation of organ-specific vasculatures requires cross-talk between developing tissue and specialized endothelial cells. Here we show how developing zebrafish spinal cord neurons coordinate vessel growth through balancing of neuron-derived Vegfaa, with neuronal sFlt1 restricting Vegfaa......-Kdrl mediated angiogenesis at the neurovascular interface. Neuron-specific loss of flt1 or increased neuronal vegfaa expression promotes angiogenesis and peri-neural tube vascular network formation. Combining loss of neuronal flt1 with gain of vegfaa promotes sprout invasion into the neural tube. On loss...... of neuronal flt1, ectopic sprouts emanate from veins involving special angiogenic cell behaviours including nuclear positioning and a molecular signature distinct from primary arterial or secondary venous sprouting. Manipulation of arteriovenous identity or Notch signalling established that ectopic sprouting...

Insulin resistance in vascular endothelial cells promotes intestinal tumour formation

DEFF Research Database (Denmark)

Wang, X; Häring, M-F; Rathjen, Thomas

2017-01-01

in vascular endothelial cells. Strikingly, these mice had 42% more intestinal tumours than controls, no change in tumour angiogenesis, but increased expression of vascular cell adhesion molecule-1 (VCAM-1) in primary culture of tumour endothelial cells. Insulin decreased VCAM-1 expression and leukocyte...... adhesion in quiescent tumour endothelial cells with intact insulin receptors and partly prevented increases in VCAM-1 and leukocyte adhesion after treatment with tumour necrosis factor-α. Knockout of insulin receptors in endothelial cells also increased leukocyte adhesion in mesenteric venules...

Bioprinting of a functional vascularized mouse thyroid gland construct.

Science.gov (United States)

Bulanova, Elena A; Koudan, Elizaveta V; Degosserie, Jonathan; Heymans, Charlotte; Pereira, Frederico DAS; Parfenov, Vladislav A; Sun, Yi; Wang, Qi; Akhmedova, Suraya A; Sviridova, Irina K; Sergeeva, Natalia S; Frank, Georgy A; Khesuani, Yusef D; Pierreux, Christophe E; Mironov, Vladimir A

2017-08-18

Bioprinting can be defined as additive biofabrication of three-dimensional (3D) tissues and organ constructs using tissue spheroids, capable of self-assembly, as building blocks. The thyroid gland, a relatively simple endocrine organ, is suitable for testing the proposed bioprinting technology. Here we report the bioprinting of a functional vascularized mouse thyroid gland construct from embryonic tissue spheroids as a proof of concept. Based on the self-assembly principle, we generated thyroid tissue starting from thyroid spheroids (TS) and allantoic spheroids (AS) as a source of thyrocytes and endothelial cells (EC), respectively. Inspired by mathematical modeling of spheroid fusion, we used an original 3D bioprinter to print TS in close association with AS within a collagen hydrogel. During the culture, closely placed embryonic tissue spheroids fused into a single integral construct, EC from AS invaded and vascularized TS, and epithelial cells from the TS progressively formed follicles. In this experimental setting, we observed formation of a capillary network around follicular cells, as observed during in utero thyroid development when thyroid epithelium controls the recruitment, invasion and expansion of EC around follicles. To prove that EC from AS are responsible for vascularization of the thyroid gland construct, we depleted endogenous EC from TS before bioprinting. EC from AS completely revascularized depleted thyroid tissue. The cultured bioprinted construct was functional as it could normalize blood thyroxine levels and body temperature after grafting under the kidney capsule of hypothyroid mice. Bioprinting of functional vascularized mouse thyroid gland construct represents a further advance in bioprinting technology, exploring the self-assembling properties of tissue spheroids.

Novel microspheres reduce the formation of deep venous thrombosis and repair the vascular wall in a rat model.

Science.gov (United States)

Dai, Bingyang; Li, Lan; Li, Qiangqiang; Song, Xiaoxiao; Chen, Dongyang; Dai, Jin; Yao, Yao; Yan, Wenjin; Teng, Huajian; Yang, Fang; Xu, Zhihong; Jiang, Qing

2017-07-01

: L-Arginine (L-arg), widely known as a substrate for endogenous nitric oxide synthesis, can improve endothelial function associated with the vasculature, inhibit platelet aggregation, and alter the activity of vascular smooth muscle cells. P-selectin is a membrane component of the platelet alpha-granule and the endothelial cell-specific Wiebel-Palade body that plays a central role in mediating interactions between platelets and both leukocytes and the endothelium. The experiment was designed to evaluate the effect of novel microspheres with L-arg targeting P-selectin on the formation of deep vein thrombosis and repair of vascular wall in a rat model. Thrombosis of the inferior vena cava was induced by applying a piece of filter paper (5 mm × 10 mm) saturated with 10% FeCl3 solution for 5 min. Targeted microspheres with L-arg, targeted microspheres with water, and saline were injected into the tail veins of the rats after 30 min of applying the filter paper saturated with 10% FeCl3 solution. The dry weight and length of the thrombus isolated from the inferior vena cava were significantly decreased in the group with L-arg in microsphere after 24 h. No significant differences in prothrombin time, activated partial thromboplastin time, thrombin time, and fibrinogen among the groups were indicated. Images revealed that apoptosis in the vascular wall was less in the group injected with targeted microspheres with L-arg than in the other two groups at 1 and 8 d postsurgery. Meanwhile, cell proliferation was considerably excessive in the group injected with L-arg wrapped in targeted microspheres. Therefore, these novel microspheres could decrease the formation of thrombus in the early stages and in the subsequent periods of thrombosis. The microspheres can also enhance the vitality of impaired endothelial cells and reduce cell apoptosis.

Pattern of Bone Generation after Irradiation in Vascularized Tissue Engineered Constructs.

Science.gov (United States)

Eweida, Ahmad; Fathi, Ibrahim; Eltawila, Ahmed M; Elsherif, Ahmad M; Elkerm, Yasser; Harhaus, Leila; Kneser, Ulrich; Sakr, Mahmoud F

2018-02-01

 Regenerative medicine modalities provide promising alternatives to conventional reconstruction techniques but are still deficient after malignant tumor excision or irradiation due to defective vascularization.  We investigated the pattern of bone formation in axially vascularized tissue engineering constructs (AVTECs) after irradiation in a study that mimics the clinical scenario after head and neck cancer. Heterotopic bone generation was induced in a subcutaneously implanted AVTEC in the thigh of six male New Zealand rabbits. The tissue construct was made up of Nanobone (Artoss GmbH; Rostock, Germany) granules mixed with autogenous bone marrow and 80 μL of bone morphogenic protein-2 at a concentration of 1.5 μg/μL. An arteriovenous loop was created microsurgically between the saphenous vessels and implanted in the core of the construct to induce axial vascularization. The constructs were subjected to external beam irradiation on postoperative day 20 with a single dose of 15 Gy. The constructs were removed 20 days after irradiation and subjected to histological and immunohistochemical analysis for vascularization, bone formation, apoptosis, and cellular proliferation.  The vascularized constructs showed homogenous vascularization and bone formation both in their central and peripheral regions. Although vascularity, proliferation, and apoptosis were similar between central and peripheral regions of the constructs, significantly more bone was formed in the central regions of the constructs.  The study shows for the first time the pattern of bone formation in AVTECs after irradiation using doses comparable to those applied after head and neck cancer. Axial vascularization probably enhances the osteoinductive properties in the central regions of AVTECs after irradiation. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Laminin promotes vascular network formation in 3D in vitro collagen scaffolds by regulating VEGF uptake.

Science.gov (United States)

Stamati, Katerina; Priestley, John V; Mudera, Vivek; Cheema, Umber

2014-09-10

Angiogenesis is an essential neovascularisation process, which if recapitulated in 3D in vitro, will provide better understanding of endothelial cell (EC) behaviour. Various cell types and growth factors are involved, with vascular endothelial growth factor (VEGF) and its receptors VEGFR1 and VEGFR2 key components. We were able to control the aggregation pattern of ECs in 3D collagen hydrogels, by varying the matrix composition and/or having a source of cells signalling angiogenic proteins. These aggregation patterns reflect the different developmental pathways that ECs take to form different sized tubular structures. Cultures with added laminin and thus increased expression of α6 integrin showed a significant increase (p3D. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Disrupted topological organization of resting-state functional brain network in subcortical vascular mild cognitive impairment.

Science.gov (United States)

Yi, Li-Ye; Liang, Xia; Liu, Da-Ming; Sun, Bo; Ying, Sun; Yang, Dong-Bo; Li, Qing-Bin; Jiang, Chuan-Lu; Han, Ying

2015-10-01

Neuroimaging studies have demonstrated both structural and functional abnormalities in widespread brain regions in patients with subcortical vascular mild cognitive impairment (svMCI). However, whether and how these changes alter functional brain network organization remains largely unknown. We recruited 21 patients with svMCI and 26 healthy control (HC) subjects who underwent resting-state functional magnetic resonance imaging scans. Graph theory-based network analyses were used to investigate alterations in the topological organization of functional brain networks. Compared with the HC individuals, the patients with svMCI showed disrupted global network topology with significantly increased path length and modularity. Modular structure was also impaired in the svMCI patients with a notable rearrangement of the executive control module, where the parietal regions were split out and grouped as a separate module. The svMCI patients also revealed deficits in the intra- and/or intermodule connectivity of several brain regions. Specifically, the within-module degree was decreased in the middle cingulate gyrus while it was increased in the left anterior insula, medial prefrontal cortex and cuneus. Additionally, increased intermodule connectivity was observed in the inferior and superior parietal gyrus, which was associated with worse cognitive performance in the svMCI patients. Together, our results indicate that svMCI patients exhibit dysregulation of the topological organization of functional brain networks, which has important implications for understanding the pathophysiological mechanism of svMCI. © 2015 John Wiley & Sons Ltd.

MMP-sensitive PEG diacrylate hydrogels with spatial variations in matrix properties stimulate directional vascular sprout formation.

Directory of Open Access Journals (Sweden)

Michael V Turturro

Full Text Available The spatial presentation of immobilized extracellular matrix (ECM cues and matrix mechanical properties play an important role in directed and guided cell behavior and neovascularization. The goal of this work was to explore whether gradients of elastic modulus, immobilized matrix metalloproteinase (MMP-sensitivity, and YRGDS cell adhesion ligands are capable of directing 3D vascular sprout formation in tissue engineered scaffolds. PEGDA hydrogels were engineered with mechanical and biofunctional gradients using perfusion-based frontal photopolymerization (PBFP. Bulk photopolymerized hydrogels with uniform mechanical properties, degradation, and immobilized biofunctionality served as controls. Gradient hydrogels exhibited an 80.4% decrease in elastic modulus and a 56.2% decrease in immobilized YRGDS. PBFP hydrogels also demonstrated gradients in hydrogel degradation with degradation times ranging from 10-12 hours in the more crosslinked regions to 4-6 hours in less crosslinked regions. An in vitro model of neovascularization, composed of co-culture aggregates of endothelial and smooth muscle cells, was used to evaluate the effect of these gradients on vascular sprout formation. Aggregate invasion in gradient hydrogels occurred bi-directionally with sprout alignment observed in the direction parallel to the gradient while control hydrogels with homogeneous properties resulted in uniform invasion. In PBFP gradient hydrogels, aggregate sprout length was found to be twice as long in the direction parallel to the gradient as compared to the perpendicular direction after three weeks in culture. This directionality was found to be more prominent in gradient regions of increased stiffness, crosslinked MMP-sensitive peptide presentation, and immobilized YRGDS concentration.

Optimization of vascularization-­inducing hydrogel bioinks for 3D bioprinting

Energy Technology Data Exchange (ETDEWEB)

Lui, E. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Moya, Monica L. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2016-09-12

This study seeks to validate the reproducibility of previous bioprinting work at Lawrence Livermore National Laboratory (LLNL) on a new Aerotech motion controller system and to modify an existing bioink, fibrin, by adding varying percent volumes of hyaluronic acid (HA). Endothelial and fibroblast cells bioprinted in fibrin gels using the Aerotech system were confirmed to be more than 77 percent viable after one day, and all bioprinted samples retained sterility after one week of culture. To characterize cell behavior in fibrin with HA addition, static co-­culture gels with varying percent volumes of HA were cultured in vitro for one week. Resulting confocal microscope images showed increased cell network formation in all concentrations of HA compared to the control (no HA), and rheological tests mimicking static gel compositions displayed positive correlations between gelation time, gel stiffness (G’), and hyaluronic acid concentration. Although the current data is insufficient to quantitatively associate HA concentration with the level of cell vascularization, future work will aim to develop a targeted HA concentration in fibrin for maximum cell network formation, to optimize the printing process parameters for this new bioink composition, and to analyze cell viability in bioprinted fibrin-­HA structures.

3D Multiscale Modelling of Angiogenesis and Vascular Tumour Growth

KAUST Repository

Perfahl, H.; Byrne, H. M.; Chen, T.; Estrella, V.; Alarcó n, T.; Lapin, A.; Gatenby, R. A.; Gillies, R. J.; Lloyd, M. C.; Maini, P. K.; Reuss, M.; Owen, M. R.

2012-01-01

We present a three-dimensional, multiscale model of vascular tumour growth, which couples nutrient/growth factor transport, blood flow, angiogenesis, vascular remodelling, movement of and interactions between normal and tumour cells, and nutrient-dependent cell cycle dynamics within each cell. We present computational simulations which show how a vascular network may evolve and interact with tumour and healthy cells. We also demonstrate how our model may be combined with experimental data, to predict the spatio-temporal evolution of a vascular tumour.

3D Multiscale Modelling of Angiogenesis and Vascular Tumour Growth

KAUST Repository

Perfahl, H.

2012-11-01

We present a three-dimensional, multiscale model of vascular tumour growth, which couples nutrient/growth factor transport, blood flow, angiogenesis, vascular remodelling, movement of and interactions between normal and tumour cells, and nutrient-dependent cell cycle dynamics within each cell. We present computational simulations which show how a vascular network may evolve and interact with tumour and healthy cells. We also demonstrate how our model may be combined with experimental data, to predict the spatio-temporal evolution of a vascular tumour.

A synergistic approach to the design, fabrication and evaluation of 3D printed micro and nano featured scaffolds for vascularized bone tissue repair

International Nuclear Information System (INIS)

Holmes, Benjamin; Bulusu, Kartik; Plesniak, Michael; Zhang, Lijie Grace

2016-01-01

3D bioprinting has begun to show great promise in advancing the development of functional tissue/organ replacements. However, to realize the true potential of 3D bioprinted tissues for clinical use requires the fabrication of an interconnected and effective vascular network. Solving this challenge is critical, as human tissue relies on an adequate network of blood vessels to transport oxygen, nutrients, other chemicals, biological factors and waste, in and out of the tissue. Here, we have successfully designed and printed a series of novel 3D bone scaffolds with both bone formation supporting structures and highly interconnected 3D microvascular mimicking channels, for efficient and enhanced osteogenic bone regeneration as well as vascular cell growth. Using a chemical functionalization process, we have conjugated our samples with nano hydroxyapatite (nHA), for the creation of novel micro and nano featured devices for vascularized bone growth. We evaluated our scaffolds with mechanical testing, hydrodynamic measurements and in vitro human mesenchymal stem cell (hMSC) adhesion (4 h), proliferation (1, 3 and 5 d) and osteogenic differentiation (1, 2 and 3 weeks). These tests confirmed bone-like physical properties and vascular-like flow profiles, as well as demonstrated enhanced hMSC adhesion, proliferation and osteogenic differentiation. Additional in vitro experiments with human umbilical vein endothelial cells also demonstrated improved vascular cell growth, migration and organization on micro-nano featured scaffolds. (paper)

A synergistic approach to the design, fabrication and evaluation of 3D printed micro and nano featured scaffolds for vascularized bone tissue repair

Science.gov (United States)

Holmes, Benjamin; Bulusu, Kartik; Plesniak, Michael; Zhang, Lijie Grace

2016-02-01

3D bioprinting has begun to show great promise in advancing the development of functional tissue/organ replacements. However, to realize the true potential of 3D bioprinted tissues for clinical use requires the fabrication of an interconnected and effective vascular network. Solving this challenge is critical, as human tissue relies on an adequate network of blood vessels to transport oxygen, nutrients, other chemicals, biological factors and waste, in and out of the tissue. Here, we have successfully designed and printed a series of novel 3D bone scaffolds with both bone formation supporting structures and highly interconnected 3D microvascular mimicking channels, for efficient and enhanced osteogenic bone regeneration as well as vascular cell growth. Using a chemical functionalization process, we have conjugated our samples with nano hydroxyapatite (nHA), for the creation of novel micro and nano featured devices for vascularized bone growth. We evaluated our scaffolds with mechanical testing, hydrodynamic measurements and in vitro human mesenchymal stem cell (hMSC) adhesion (4 h), proliferation (1, 3 and 5 d) and osteogenic differentiation (1, 2 and 3 weeks). These tests confirmed bone-like physical properties and vascular-like flow profiles, as well as demonstrated enhanced hMSC adhesion, proliferation and osteogenic differentiation. Additional in vitro experiments with human umbilical vein endothelial cells also demonstrated improved vascular cell growth, migration and organization on micro-nano featured scaffolds.

Imaging after vascular gene therapy

International Nuclear Information System (INIS)

Manninen, Hannu I.; Yang, Xiaoming

2005-01-01

Targets for cardiovascular gene therapy currently include limiting restenosis after balloon angioplasty and stent placement, inhibiting vein bypass graft intimal hyperplasia/stenosis, therapeutic angiogenesis for cardiac and lower-limb ischemia, and prevention of thrombus formation. While catheter angiography is still standard method to follow-up vascular gene transfer, other modern imaging techniques, especially intravascular ultrasound (IVUS), magnetic resonance (MR), and positron emission tomography (PET) imaging provide complementary information about the therapeutic effect of vascular gene transfer in humans. Although molecular imaging of therapeutic gene expression in the vasculatures is still in its technical development phase, it has already offered basic medical science an extremely useful in vivo evaluation tool for non- or minimally invasive imaging of vascular gene therapy

A first vascularized skin equivalent as an alternative to animal experimentation.

Science.gov (United States)

Groeber, Florian; Engelhardt, Lisa; Lange, Julia; Kurdyn, Szymon; Schmid, Freia F; Rücker, Christoph; Mielke, Stephan; Walles, Heike; Hansmann, Jan

2016-01-01

Tissue-engineered skin equivalents mimic key aspects of the human skin, and can thus be employed as wound coverage for large skin defects or as in vitro test systems as an alternative to animal models. However, current skin equivalents lack a functional vasculature limiting clinical and research applications. This study demonstrates the generation of a vascularized skin equivalent with a perfused vascular network by combining a biological vascularized scaffold (BioVaSc) based on a decellularized segment of a porcine jejunum and a tailored bioreactor system. Briefly, the BioVaSc was seeded with human fibroblasts, keratinocytes, and human microvascular endothelial cells. After 14 days at the air-liquid interface, hematoxylin & eosin and immunohistological staining revealed a specific histological architecture representative of the human dermis and epidermis including a papillary-like architecture at the dermal-epidermal-junction. The formation of the skin barrier was measured non-destructively using impedance spectroscopy. Additionally, endothelial cells lined the walls of the formed vessels that could be perfused with a physiological volume flow. Due to the presence of a complex in-vivo-like vasculature, the here shown skin equivalent has the potential for skin grafting and represents a sophisticated in vitro model for dermatological research.

Causal biological network database: a comprehensive platform of causal biological network models focused on the pulmonary and vascular systems.

Science.gov (United States)

Boué, Stéphanie; Talikka, Marja; Westra, Jurjen Willem; Hayes, William; Di Fabio, Anselmo; Park, Jennifer; Schlage, Walter K; Sewer, Alain; Fields, Brett; Ansari, Sam; Martin, Florian; Veljkovic, Emilija; Kenney, Renee; Peitsch, Manuel C; Hoeng, Julia

2015-01-01

With the wealth of publications and data available, powerful and transparent computational approaches are required to represent measured data and scientific knowledge in a computable and searchable format. We developed a set of biological network models, scripted in the Biological Expression Language, that reflect causal signaling pathways across a wide range of biological processes, including cell fate, cell stress, cell proliferation, inflammation, tissue repair and angiogenesis in the pulmonary and cardiovascular context. This comprehensive collection of networks is now freely available to the scientific community in a centralized web-based repository, the Causal Biological Network database, which is composed of over 120 manually curated and well annotated biological network models and can be accessed at http://causalbionet.com. The website accesses a MongoDB, which stores all versions of the networks as JSON objects and allows users to search for genes, proteins, biological processes, small molecules and keywords in the network descriptions to retrieve biological networks of interest. The content of the networks can be visualized and browsed. Nodes and edges can be filtered and all supporting evidence for the edges can be browsed and is linked to the original articles in PubMed. Moreover, networks may be downloaded for further visualization and evaluation. Database URL: http://causalbionet.com © The Author(s) 2015. Published by Oxford University Press.

Adapted Boolean network models for extracellular matrix formation

Directory of Open Access Journals (Sweden)

Wollbold Johannes

2009-07-01

Full Text Available Abstract Background Due to the rapid data accumulation on pathogenesis and progression of chronic inflammation, there is an increasing demand for approaches to analyse the underlying regulatory networks. For example, rheumatoid arthritis (RA is a chronic inflammatory disease, characterised by joint destruction and perpetuated by activated synovial fibroblasts (SFB. These abnormally express and/or secrete pro-inflammatory cytokines, collagens causing joint fibrosis, or tissue-degrading enzymes resulting in destruction of the extra-cellular matrix (ECM. We applied three methods to analyse ECM regulation: data discretisation to filter out noise and to reduce complexity, Boolean network construction to implement logic relationships, and formal concept analysis (FCA for the formation of minimal, but complete rule sets from the data. Results First, we extracted literature information to develop an interaction network containing 18 genes representing ECM formation and destruction. Subsequently, we constructed an asynchronous Boolean network with biologically plausible time intervals for mRNA and protein production, secretion, and inactivation. Experimental gene expression data was obtained from SFB stimulated by TGFβ1 or by TNFα and discretised thereafter. The Boolean functions of the initial network were improved iteratively by the comparison of the simulation runs to the experimental data and by exploitation of expert knowledge. This resulted in adapted networks for both cytokine stimulation conditions. The simulations were further analysed by the attribute exploration algorithm of FCA, integrating the observed time series in a fine-tuned and automated manner. The resulting temporal rules yielded new contributions to controversially discussed aspects of fibroblast biology (e.g., considerable expression of TNF and MMP9 by fibroblasts stimulation and corroborated previously known facts (e.g., co-expression of collagens and MMPs after TNF�

Network formation in a multi-asset artificial stock market

Science.gov (United States)

Wu, Songtao; He, Jianmin; Li, Shouwei; Wang, Chao

2018-04-01

A multi-asset artificial stock market is developed. In the market, stocks are assigned to a number of sectors and traded by heterogeneous investors. The mechanism of continuous double auction is employed to clear order book and form daily closed prices. Simulation results of prices at the sector level show an intra-sector similarity and inter-sector distinctiveness, and returns of individual stocks have stylized facts that are ubiquitous in the real-world stock market. We find that the market risk factor has critical impact on both network topology transition and connection formation, and that sector risk factors account for the formation of intra-sector links and sector-based local interaction. In addition, the number of community in threshold-based networks is correlated negatively and positively with the value of correlation coefficients and the ratio of intra-sector links, which are respectively determined by intensity of sector risk factors and the number of sectors.

Vascular retraction driven by matrix softening

Science.gov (United States)

Valentine, Megan

We recently discovered we can directly apply physical forces and monitor the downstream responses in a living organism in real time through manipulation of the blood vessels of a marine organism called, Botryllus schlosseri. The extracellular matrix (ECM) plays a key role in regulating vascular growth and homeostasis in Botryllus,a basal chordate which has a large, transparent extracorporeal vascular network that can encompass areas >100 cm2. We have determined that lysyl oxidase 1 (LOX1), which is responsible for cross-linking collagen, is expressed in all vascular cells and is critically important for vascular maintenance. Inhibition of LOX1 activity in vivo by the addition of a specific inhibitor, ß-aminopropionitrile (BAPN), caused a rapid, global regression of the entire vascular bed, with some vessels regressing >10 mm within 16 hrs. In this talk, I will discuss the molecular and cellular origins of this systemic remodeling event, which hinges upon the ability of the vascular cells to sense and respond to mechanical signals, while introducing this exciting new model system for studies of biological physics and mechanobiology. Collaborators: Anthony DeTomaso, Delany Rodriguez, Aimal Khankhel (UCSB).

Opinion formation in a social network: The role of human activity

Science.gov (United States)

Grabowski, Andrzej

2009-03-01

The model of opinion formation in human population based on social impact theory is investigated numerically. On the basis of a database received from the on-line game server, we examine the structure of social network and human dynamics. We calculate the activity of individuals, i.e. the relative time devoted daily to interactions with others in the artificial society. We study the influence of correlation between the activity of an individual and its connectivity on the process of opinion formation. We find that such correlations have a significant influence on the temperature of the phase transition and the effect of the mass media, modeled as an external stimulation acting on the social network.

Inter-organizational relationships: promoters and restrictive factors in the formation of cooperation network

Directory of Open Access Journals (Sweden)

Marcos Antonio Gaspar

2014-04-01

Full Text Available The present paper had as aim to identify factors of inter-organizational relationships which promotes and restricts the formation of companies’ cooperation network, from two levels of analysis (organizational and inter-organizational. To achieve this goal, it was developed a descriptive-qualitative study, with prospecting for primary and secondary data on a cooperation network. The universe was composed by 41 participating companies associated to the analyzed network. The sampling procedure was for researcher’s accessibility and convenience. As a result, it was identified that the network is guided by goals of cooperation among the participating companies, in addition to representing the sector and provide services in the interests of the associates. The main factors influencing the formation of the network were: business center, marketing and training; but only training has been achieved satisfactorily. The business center and marketing factors have not yet been fully developed, being both identified as restrictive factors.

Automatic modulation format recognition for the next generation optical communication networks using artificial neural networks

Science.gov (United States)

Guesmi, Latifa; Hraghi, Abir; Menif, Mourad

2015-03-01

A new technique for Automatic Modulation Format Recognition (AMFR) in next generation optical communication networks is presented. This technique uses the Artificial Neural Network (ANN) in conjunction with the features of Linear Optical Sampling (LOS) of the detected signal at high bit rates using direct detection or coherent detection. The use of LOS method for this purpose mainly driven by the increase of bit rates which enables the measurement of eye diagrams. The efficiency of this technique is demonstrated under different transmission impairments such as chromatic dispersion (CD) in the range of -500 to 500 ps/nm, differential group delay (DGD) in the range of 0-15 ps and the optical signal tonoise ratio (OSNR) in the range of 10-30 dB. The results of numerical simulation for various modulation formats demonstrate successful recognition from a known bit rates with a higher estimation accuracy, which exceeds 99.8%.

Vector-based RNA interference against vascular endothelial growth factor-A significantly limits vascularization and growth of prostate cancer in vivo.

Science.gov (United States)

Wannenes, Francesca; Ciafré, Silvia Anna; Niola, Francesco; Frajese, Gaetano; Farace, Maria Giulia

2005-12-01

RNA interference technology is emerging as a very potent tool to obtain a cellular knockdown of a desired gene. In this work we used vector-based RNA interference to inhibit vascular endothelial growth factor (VEGF) expression in prostate cancer in vitro and in vivo. We demonstrated that transduction with a plasmid carrying a small interfering RNA targeting all isoforms of VEGF, dramatically impairs the expression of this growth factor in the human prostate cancer cell line PC3. As a consequence, PC3 cells loose their ability to induce one of the fundamental steps of angiogenesis, namely the formation of a tube-like network in vitro. Most importantly, our "therapeutic" vector is able to impair tumor growth rate and vascularization in vivo. We show that a single injection of naked plasmid in developing neoplastic mass significantly decreases microvessel density in an androgen-refractory prostate xenograft and is able to sustain a long-term slowing down of tumor growth. In conclusion, our results confirm the basic role of VEGF in the angiogenic development of prostate carcinoma, and suggest that the use of our vector-based RNA interference approach to inhibit angiogenesis could be an effective tool in view of future gene therapy applications for prostate cancer.

Piperlongumine inhibits atherosclerotic plaque formation and vascular smooth muscle cell proliferation by suppressing PDGF receptor signaling

Energy Technology Data Exchange (ETDEWEB)

Son, Dong Ju [Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (United States); Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA (United States); Kim, Soo Yeon [Division of Life Science, Korea Basic Science Institute, Daejeon (Korea, Republic of); Han, Seong Su [University of Iowa Carver College of Medicine, Department of Pathology, Iowa City, IA (United States); Kim, Chan Woo [Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (United States); Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA (United States); Department of Bioinspired Science, Ehwa Womans University, Seoul (Korea, Republic of); Kumar, Sandeep [Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (United States); Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA (United States); Park, Byeoung Soo [Nanotoxtech Co., Ansan (Korea, Republic of); Lee, Sung Eun [Division of Applied Biology and Chemistry, Kyungpook National University, Daegu (Korea, Republic of); Yun, Yeo Pyo [College of Pharmacy, Chungbuk National University, Cheongju (Korea, Republic of); Jo, Hanjoong, E-mail: hjo@emory.edu [Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (United States); Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA (United States); Department of Bioinspired Science, Ehwa Womans University, Seoul (Korea, Republic of); Park, Young Hyun, E-mail: pyh012@sch.ac.kr [Department of Food Science and Nutrition, College of Natural Sciences, Soonchunhyang University, Asan (Korea, Republic of)

2012-10-19

Highlights: Black-Right-Pointing-Pointer Anti-atherogenic effect of PL was examined using partial carotid ligation model in ApoE KO mice. Black-Right-Pointing-Pointer PL prevented atherosclerotic plaque development, VSMCs proliferation, and NF-{kappa}B activation. Black-Right-Pointing-Pointer Piperlongumine reduced vascular smooth muscle cell activation through PDGF-R{beta} and NF-{kappa}B-signaling. Black-Right-Pointing-Pointer PL may serve as a new therapeutic molecule for atherosclerosis treatment. -- Abstract: Piperlongumine (piplartine, PL) is an alkaloid found in the long pepper (Piper longum L.) and has well-documented anti-platelet aggregation, anti-inflammatory, and anti-cancer properties; however, the role of PL in prevention of atherosclerosis is unknown. We evaluated the anti-atherosclerotic potential of PL in an in vivo murine model of accelerated atherosclerosis and defined its mechanism of action in aortic vascular smooth muscle cells (VSMCs) in vitro. Local treatment with PL significantly reduced atherosclerotic plaque formation as well as proliferation and nuclear factor-kappa B (NF-{kappa}B) activation in an in vivo setting. PL treatment in VSMCs in vitro showed inhibition of migration and platelet-derived growth factor BB (PDGF-BB)-induced proliferation to the in vivo findings. We further identified that PL inhibited PDGF-BB-induced PDGF receptor beta activation and suppressed downstream signaling molecules such as phospholipase C{gamma}1, extracellular signal-regulated kinases 1 and 2 and Akt. Lastly, PL significantly attenuated activation of NF-{kappa}B-a downstream transcriptional regulator in PDGF receptor signaling, in response to PDGF-BB stimulation. In conclusion, our findings demonstrate a novel, therapeutic mechanism by which PL suppresses atherosclerosis plaque formation in vivo.

Guidance of vascular development: lessons from the nervous system.

Science.gov (United States)

Larrivée, Bruno; Freitas, Catarina; Suchting, Steven; Brunet, Isabelle; Eichmann, Anne

2009-02-27

The vascular system of vertebrates consists of an organized, branched network of arteries, veins, and capillaries that penetrates all the tissues of the body. One of the most striking features of the vascular system is that its branching pattern is highly stereotyped, with major and secondary branches forming at specific sites and developing highly conserved organ-specific vascular patterns. The factors controlling vascular patterning are not yet completely understood. Recent studies have highlighted the anatomic and structural similarities between blood vessels and nerves. The 2 networks are often aligned, with nerve fibers and blood vessels following parallel routes. Furthermore, both systems require precise control over their guidance and growth. Several molecules with attractive and repulsive properties have been found to modulate the proper guidance of both nerves and blood vessels. These include the Semaphorins, the Slits, and the Netrins and their receptors. In this review, we describe the molecular mechanisms by which blood vessels and axons achieve proper path finding and the molecular cues that are involved in their guidance.

Mathematical Analysis of a PDE System for Biological Network Formation

KAUST Repository

Haskovec, Jan; Markowich, Peter A.; Perthame, Benoit

2015-01-01

Motivated by recent physics papers describing rules for natural network formation, we study an elliptic-parabolic system of partial differential equations proposed by Hu and Cai [13, 15]. The model describes the pressure field thanks to Darcy's type

[Infectious risk related to the formation of multi-species biofilms (Candida - bacteria) on peripheral vascular catheters].

Science.gov (United States)

Seghir, A; Boucherit-Otmani, Z; Sari-Belkharroubi, L; Boucherit, K

2017-03-01

The Candida yeasts are the fourth leading cause of death from systemic infections, the risk may increase when the infection also involves bacteria. Yeasts and bacteria can adhere to medical implants, such as peripheral vascular catheters, and form a multicellular structures called "mixed biofilms" more resistant to antimicrobials agents. However, the formation of mixed biofilms on implants leads to long-term persistent infections because they can act as reservoirs of pathogens that have poorly understood interactions. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

A network architecture for precision formation flying using the IEEE 802.11 MAC Protocol

Science.gov (United States)

Clare, Loren P.; Gao, Jay L.; Jennings, Esther H.; Okino, Clayton

2005-01-01

Precision Formation Flying missions involve the tracking and maintenance of spacecraft in a desired geometric formation. The strong coupling of spacecraft in formation flying control requires inter-spacecraft communication to exchange information. In this paper, we present a network architecture that supports PFF control, from the initial random deployment phase to the final formation. We show that a suitable MAC layer for the application protocol is IEEE's 802.11 MAC protocol. IEEE 802.11 MAC has two modes of operations: DCF and PCF. We show that DCF is suitable for the initial deployment phase while switching to PCF when the spacecraft are in formation improves jitter and throughput. We also consider the effect of routing on protocol performance and suggest when it is profitable to turn off route discovery to achieve better network performance.

Mural cell associated VEGF is required for organotypic vessel formation.

Directory of Open Access Journals (Sweden)

Lasse Evensen

Full Text Available BACKGROUND: Blood vessels comprise endothelial cells, mural cells (pericytes/vascular smooth muscle cells and basement membrane. During angiogenesis, mural cells are recruited to sprouting endothelial cells and define a stabilizing context, comprising cell-cell contacts, secreted growth factors and extracellular matrix components, that drives vessel maturation and resistance to anti-angiogenic therapeutics. METHODS AND FINDINGS: To better understand the basis for mural cell regulation of angiogenesis, we conducted high content imaging analysis on a microtiter plate format in vitro organotypic blood vessel system comprising primary human endothelial cells co-cultured with primary human mural cells. We show that endothelial cells co-cultured with mural cells undergo an extensive series of phenotypic changes reflective of several facets of blood vessel formation and maturation: Loss of cell proliferation, pathfinding-like cell migration, branching morphogenesis, basement membrane extracellular matrix protein deposition, lumen formation, anastamosis and development of a stabilized capillary-like network. This phenotypic sequence required endothelial-mural cell-cell contact, mural cell-derived VEGF and endothelial VEGFR2 signaling. Inhibiting formation of adherens junctions or basement membrane structures abrogated network formation. Notably, inhibition of mural cell VEGF expression could not be rescued by exogenous VEGF. CONCLUSIONS: These results suggest a unique role for mural cell-associated VEGF in driving vessel formation and maturation.

Formation Features of the Customer Segments for the Network Organizations in the Smart Era

Directory of Open Access Journals (Sweden)

Elena V. Yaroshenko

2017-01-01

Full Text Available Modern network society is based on the advances of information era of Smart, connecting information and communication technologies, intellectual resources and new forms of managing in the global electronic space. It leads to domination of network forms of the organization of economic activity. Many experts prove the importance of segmentation process of consumers when developing competitive strategy of the organization. Every company needs a competent segmentation of the customer base, allowing to concentrate the attention on satisfaction of requirements of the most perspective client segments. The network organizations have specific characteristics; therefore, it is important to understand how they can influence on the formation of client profiles. It causes the necessity of the network organizations’ research in terms of management of high-profitable client segments.The aim of this study is to determine the characteristics of the market segmentation and to choose the key customers for the network organizations. This purpose has defined the statement and the solution of the following tasks: to explore characteristic features of the network forms of the organization of economic activity of the companies, their prospects, Smart technologies’ influence on them; to reveal the work importance with different client profiles; to explore the existing methods and tools of formation of key customer segments; to define criteria for selection of key groups; to reveal the characteristics of customer segments’ formation for the network organizations.In the research process, methods of the system analysis, a method of analogies, methods of generalizations, a method of the expert evaluations, methods of classification and clustering were applied.This paper explores the characteristics and principles of functioning of network organizations, the appearance of which is directly linked with the development of Smart society. It shows the influence on the

VEGF-A, cytoskeletal dynamics, and the pathological vascular phenotype

International Nuclear Information System (INIS)

Nagy, Janice A.; Senger, Donald R.

2006-01-01

Normal angiogenesis is a complex process involving the organization of proliferating and migrating endothelial cells (ECs) into a well-ordered and highly functional vascular network. In contrast, pathological angiogenesis, which is a conspicuous feature of tumor growth, ischemic diseases, and chronic inflammation, is characterized by vessels with aberrant angioarchitecture and compromised barrier function. Herein we review the subject of pathological angiogenesis, particularly that driven by vascular endothelial growth factor (VEGF-A), from a new perspective. We propose that the serious structural and functional anomalies associated with VEGF-A-elicited neovessels, reflect, at least in part, imbalances in the internal molecular cues that govern the ordered assembly of ECs into three dimensional vascular networks and preserve vessel barrier function. Adopting such a viewpoint widens the focus from solely on specific pro-angiogenic stimuli such as VEGF-A to include a key set of cytoskeletal regulatory molecules, the Rho GTPases, which are known to direct multiple aspects of vascular morphogenesis including EC motility, alignment, multi-cellular organization, as well as intercellular junction integrity. We offer this perspective to draw attention to the importance of endothelial cytoskeletal dynamics for proper neovascularization and to suggest new therapeutic strategies with the potential to improve the pathological vascular phenotype

C60-pentacene network formation by 2-D co-crystallization.

Science.gov (United States)

Jin, Wei; Dougherty, Daniel B; Cullen, William G; Robey, Steven; Reutt-Robey, Janice E

2009-09-01

We report experiments highlighting the mechanistic role of mobile pentacene precursors in the formation of a network C(60)-pentacene co-crystalline structure on Ag(111). This co-crystalline arrangement was first observed by low temperature scanning tunneling microscopy (STM) by Zhang et al. (Zhang, H. L.; Chen, W.; Huang, H.; Chen, L.; Wee, A. T. S. J. Am. Chem. Soc. 2008, 130, 2720-2721). We now show that this structure forms readily at room temperature from a two-dimensional (2-D) mixture. Pentacene, evaporated onto Ag(111) to coverages of 0.4-1.0 ML, produces a two-dimensional (2-D) gas. Subsequently deposited C(60) molecules combine with the pentacene 2-D gas to generate a network structure, consisting of chains of close-packed C(60) molecules, spaced by individual C(60) linkers and 1 nm x 2.5 nm pores containing individual pentacene molecules. Spontaneous formation of this stoichiometric (C(60))(4)-pentacene network from a range of excess pentacene surface coverage (0.4 to 1.0 ML) indicates a self-limiting assembly process. We refine the structure model for this phase and discuss the generality of this co-crystallization mechanism.

Molecular parallels between neural and vascular development.

Science.gov (United States)

Eichmann, Anne; Thomas, Jean-Léon

2013-01-01

The human central nervous system (CNS) features a network of ~400 miles of blood vessels that receives >20% of the body's cardiac output and uses most of its blood glucose. Many human diseases, including stroke, retinopathy, and cancer, are associated with the biology of CNS blood vessels. These vessels originate from extrinsic cell populations, including endothelial cells and pericytes that colonize the CNS and interact with glia and neurons to establish the blood-brain barrier and control cerebrovascular exchanges. Neurovascular interactions also play important roles in adult neurogenic niches, which harbor a unique population of neural stem cells that are intimately associated with blood vessels. We here review the cellular and molecular mechanisms required to establish the CNS vascular network, with a special focus on neurovascular interactions and the functions of vascular endothelial growth factors.

Formation of DNA-network embedding ferromagnetic Cobalt nano-particles

Science.gov (United States)

Kanki, Teruo; Tanaka, Hidekazu; Shirakawa, Hideaki; Sacho, Yu; Taniguchi, Masateru; Lee, Hea-Yeon; Kawai, Tomoji; Kang, Nam-Jung; Chen, Jinwoo

2002-03-01

Formation of DNA-network embedding ferromagnetic Cobalt nano-particles T. Kanki, Hidekazu. Tanaka, H. Shirakawa, Y. Sacho, M. Taniguchi, H. Lee, T. Kawai The Institute of Scientific and Industrial Research, Osaka University, Japan and Nam-Jung Kang, Jinwoo Chen Korea Advanced Institute of Science and Technology (KAIST), Korea DNA can be regarded as a naturally occurring and highly specific functional biopolymer and as a fine nano-wire. Moreover, it was found that large-scale DNA networks can be fabricated on mica surfaces. By using this network structure, we can expect to construct nano-scale assembly of functional nano particle, for example ferromagnetic Co nano particles, toward nano scale spin-electronics based on DNA circuits. When we formed DNA network by 250mg/ml DNA solution of poly(dG)-poly(dC) including ferromagnetic Co nano particles (diameter of 12nm), we have conformed the DNA network structure embedding Co nano-particles (height of about 12nm) by atomic force microscopy. On the other hand, we used 100mg/ml DNA solution, DNA can not connect each other, and many Co nano-particles exist without being embedded.

EXPLORING THE RELATIONSHIPS AMONG SOCIAL BENEFITS, ONLINE SOCIAL NETWORK DEPENDENCY, SATISFACTION, AND YOUTH’S HABIT FORMATION

Directory of Open Access Journals (Sweden)

Tran Van Dat

2015-12-01

Full Text Available Online social network is one of the biggest Internet phenomenon, which has attracted the interest of many marketers and psychologists who wanted to understand social network users’ behavior. Recognizing the lack of theoretical and empirical attention that has been given to this field, especially in Vietnam market, this study was conducted to examine the relationships among social benefits, online social network dependency, satisfaction, and youth’s habit formation in the context of Facebook. The findings of the study of 200 Facebook users indicated that the interrelationship among four factors of social benefits, online social network dependency, satisfaction, and habit formation affect each other. Indeed, dependency on online social network among the youth whose age ranged from 16 to 24 years old is significantly affected by social benefits factor and leads to the formation of habit. In addition, satisfaction plays a role in determining habitual Facebook use. This paper discusses theoretical and practical implication in marketing and psychology field.

Augmentation of radiation response with the vascular targeting agent ZD6126

International Nuclear Information System (INIS)

Hoang Tien; Huang Shyhmin; Armstrong, Eric; Eickhoff, Jens C.; Harari, Paul M.

2006-01-01

Purpose: To examine the antivascular and antitumor activity of the vascular targeting agent ZD6126 in combination with radiation in lung and head-and-neck (H and N) cancer models. The overall hypothesis was that simultaneous targeting of tumor cells (radiation) and tumor vasculature (ZD6126) might enhance tumor cell killing. Methods and Materials: A series of in vitro studies using human umbilical vein endothelial cells (HUVEC) and in vivo studies in athymic mice bearing human lung (H226) and H and N (squamous cell carcinoma [SCC]1, SCC6) tumor xenografts treated with ZD6126 and/or radiation were performed. Results: ZD6126 inhibited the capillary-like network formation in HUVEC. Treatment of HUVEC with ZD6126 resulted in cell cycle arrest in G2/M, with decrease of cells in S phase and proliferation inhibition in a dose-dependent manner. ZD6126 augmented the cell-killing effect of radiation and radiation-induced apoptosis in HUVEC. The combination of ZD6126 and radiation further decreased tumor vascularization in an in vivo Matrigel angiogenesis assay. In tumor xenografts, ZD6126 enhanced the antitumor activity of radiation, resulting in tumor growth delay. Conclusions: These preclinical studies suggest that ZD6126 can augment the radiation response of proliferating endothelial H and N and lung cancer cells. These results complement recent reports suggesting the potential value of combining radiation with vascular targeting/antiangiogenic agents

Neural Network Observer-Based Finite-Time Formation Control of Mobile Robots

Directory of Open Access Journals (Sweden)

Caihong Zhang

2014-01-01

Full Text Available This paper addresses the leader-following formation problem of nonholonomic mobile robots. In the formation, only the pose (i.e., the position and direction angle of the leader robot can be obtained by the follower. First, the leader-following formation is transformed into special trajectory tracking. And then, a neural network (NN finite-time observer of the follower robot is designed to estimate the dynamics of the leader robot. Finally, finite-time formation control laws are developed for the follower robot to track the leader robot in the desired separation and bearing in finite time. The effectiveness of the proposed NN finite-time observer and the formation control laws are illustrated by both qualitative analysis and simulation results.

Photoacoustic imaging of vascular networks in transgenic mice

Science.gov (United States)

Laufer, J. G.; Cleary, J. O.; Zhang, E. Z.; Lythgoe, M. F.; Beard, P. C.

2010-02-01

The preferential absorption of near infrared light by blood makes photoacoustic imaging well suited to visualising vascular structures in soft tissue. In addition, the spectroscopic specificity of tissue chromophores can be exploited by acquiring images at multiple excitation wavelengths. This allows the quantification of endogenous chromophores, such as oxy- and deoxyhaemoglobin, and hence blood oxygenation, and the detection of exogenous chromophores, such as functionalised contrast agents. More importantly, this approach has the potential to visualise the spatial distribution of low concentrations of functionalised contrast agents against the strong background absorption of the endogenous chromophores. This has a large number of applications in the life sciences. One example is the structural and functional phenotyping of transgenic mice for the study of the genetic origins of vascular malformations, such as heart defects. In this study, photoacoustic images of mouse embryos have been acquired to study the development of the vasculature following specific genetic knockouts.

Engineering the mechanical and biological properties of nanofibrous vascular grafts for in situ vascular tissue engineering.

Science.gov (United States)

Henry, Jeffrey J D; Yu, Jian; Wang, Aijun; Lee, Randall; Fang, Jun; Li, Song

2017-08-17

Synthetic small diameter vascular grafts have a high failure rate, and endothelialization is critical for preventing thrombosis and graft occlusion. A promising approach is in situ tissue engineering, whereby an acellular scaffold is implanted and provides stimulatory cues to guide the in situ remodeling into a functional blood vessel. An ideal scaffold should have sufficient binding sites for biomolecule immobilization and a mechanical property similar to native tissue. Here we developed a novel method to blend low molecular weight (LMW) elastic polymer during electrospinning process to increase conjugation sites and to improve the mechanical property of vascular grafts. LMW elastic polymer improved the elasticity of the scaffolds, and significantly increased the amount of heparin conjugated to the micro/nanofibrous scaffolds, which in turn increased the loading capacity of vascular endothelial growth factor (VEGF) and prolonged the release of VEGF. Vascular grafts were implanted into the carotid artery of rats to evaluate the in vivo performance. VEGF treatment significantly enhanced endothelium formation and the overall patency of vascular grafts. Heparin coating also increased cell infiltration into the electrospun grafts, thus increasing the production of collagen and elastin within the graft wall. This work demonstrates that LMW elastic polymer blending is an approach to engineer the mechanical and biological property of micro/nanofibrous vascular grafts for in situ vascular tissue engineering.

Self-Replenishing Vascularized Fouling-Release Surfaces

Energy Technology Data Exchange (ETDEWEB)

Howell, C; Vu, TL; Lin, JJ; Kolle, S; Juthani, N; Watson, E; Weaver, JC; Alvarenga, J; Aizenberg, J

2014-08-13

Inspired by the long-term effectiveness of living antifouling materials, we have developed a method for the self-replenishment of synthetic biofouling-release surfaces. These surfaces are created by either molding or directly embedding 3D vascular systems into polydimethylsiloxane (PDMS) and filling them with a silicone oil to generate a nontoxic oil-infused material. When replenished with silicone oil from an outside source, these materials are capable of self-lubrication and continuous renewal of the interfacial fouling-release layer. Under accelerated lubricant loss conditions, fully infused vascularized samples retained significantly more lubricant than equivalent nonvascularized controls. Tests of lubricant-infused PDMS in static cultures of the infectious bacteria Staphylococcus aureus and Escherichia coli as well as the green microalgae Botryococcus braunii, Chlamydomonas reinhardtii, Dunaliella sauna, and Nannochloropsis oculata showed a significant reduction in biofilm adhesion compared to PDMS and glass controls containing no lubricant. Further experiments on vascularized versus nonvascularized samples that had been subjected to accelerated lubricant evaporation conditions for up to 48 h showed significantly less biofilm adherence on the vascularized surfaces. These results demonstrate the ability of an embedded lubricant-filled vascular network to improve the longevity of fouling-release surfaces.

Directed networks' different link formation mechanisms causing degree distribution distinction

Science.gov (United States)

Behfar, Stefan Kambiz; Turkina, Ekaterina; Cohendet, Patrick; Burger-Helmchen, Thierry

2016-11-01

Within undirected networks, scientists have shown much interest in presenting power-law features. For instance, Barabási and Albert (1999) claimed that a common property of many large networks is that vertex connectivity follows scale-free power-law distribution, and in another study Barabási et al. (2002) showed power law evolution in the social network of scientific collaboration. At the same time, Jiang et al. (2011) discussed deviation from power-law distribution; others indicated that size effect (Bagrow et al., 2008), information filtering mechanism (Mossa et al., 2002), and birth and death process (Shi et al., 2005) could account for this deviation. Within directed networks, many authors have considered that outlinks follow a similar mechanism of creation as inlinks' (Faloutsos et al., 1999; Krapivsky et al., 2001; Tanimoto, 2009) with link creation rate being the linear function of node degree, resulting in a power-law shape for both indegree and outdegree distribution. Some other authors have made an assumption that directed networks, such as scientific collaboration or citation, behave as undirected, resulting in a power-law degree distribution accordingly (Barabási et al., 2002). At the same time, we claim (1) Outlinks feature different degree distributions than inlinks; where different link formation mechanisms cause the distribution distinctions, (2) in/outdegree distribution distinction holds for different levels of system decomposition; therefore this distribution distinction is a property of directed networks. First, we emphasize in/outlink formation mechanisms as causal factors for distinction between indegree and outdegree distributions (where this distinction has already been noticed in Barker et al. (2010) and Baxter et al. (2006)) within a sample network of OSS projects as well as Java software corpus as a network. Second, we analyze whether this distribution distinction holds for different levels of system decomposition: open

Critical role of nucleotide-binding oligomerization domain-like receptor 3 in vascular repair

International Nuclear Information System (INIS)

Schlaweck, Sebastian; Zimmer, Sebastian; Struck, Rafael; Bartok, Eva; Werner, Nikos; Bauernfeind, Franz; Latz, Eicke; Nickenig, Georg; Hornung, Veit; Ghanem, Alexander

2011-01-01

Highlights: → NLRP3 is not required for systemic cardiovascular function in healthy mice. → NLRP3 deficiency itself does not affect the functional cardiovascular phenotype and that it does not alter peripheral differential blood counts. → NLRP3 is critical in neointima formation following vascular injury. -- Abstract: Vascular remodeling characterized by hyperproliferative neointima formation is an unfavorable repair process that is triggered by vascular damage. This process is characterized by an increased local inflammatory and proliferative response that critically involves the pro-inflammatory cytokine interleukin-1β (IL-1β). IL-1β is expressed and cytosolically retained as a procytokine that requires additional processing prior to exerting its pro-inflammatory function. Maturation and release of pro IL-1β is governed by a cytosolic protein scaffold that is known as the inflammasome. Here we show that NLRP3 (NOD-like receptor family, pryin domain containing 3), an important activating component of the inflammasome, is involved in neointima formation after vascular injury. NLRP3 deficiency itself does not affect the functional cardiovascular phenotype and does not alter peripheral differential blood counts. However, neointima development following wire injury of the carotid artery was significantly decreased in NLRP3-deficient mice as compared to wild-type controls. In all, NLRP3 plays a non-redundant role in vascular damage mediated neointima formation. Our data establish NLRP3 as a key player in the response to vascular damage, which could open new avenues to therapeutic intervention.

Critical role of nucleotide-binding oligomerization domain-like receptor 3 in vascular repair

Energy Technology Data Exchange (ETDEWEB)

Schlaweck, Sebastian; Zimmer, Sebastian; Struck, Rafael [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Bartok, Eva [Institute for Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Werner, Nikos [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Bauernfeind, Franz [Institute for Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Latz, Eicke [Institute of Innate Immunity, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Nickenig, Georg [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Hornung, Veit [Institute for Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Ghanem, Alexander, E-mail: ghanem@uni-bonn.de [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany)

2011-08-05

Highlights: {yields} NLRP3 is not required for systemic cardiovascular function in healthy mice. {yields} NLRP3 deficiency itself does not affect the functional cardiovascular phenotype and that it does not alter peripheral differential blood counts. {yields} NLRP3 is critical in neointima formation following vascular injury. -- Abstract: Vascular remodeling characterized by hyperproliferative neointima formation is an unfavorable repair process that is triggered by vascular damage. This process is characterized by an increased local inflammatory and proliferative response that critically involves the pro-inflammatory cytokine interleukin-1{beta} (IL-1{beta}). IL-1{beta} is expressed and cytosolically retained as a procytokine that requires additional processing prior to exerting its pro-inflammatory function. Maturation and release of pro IL-1{beta} is governed by a cytosolic protein scaffold that is known as the inflammasome. Here we show that NLRP3 (NOD-like receptor family, pryin domain containing 3), an important activating component of the inflammasome, is involved in neointima formation after vascular injury. NLRP3 deficiency itself does not affect the functional cardiovascular phenotype and does not alter peripheral differential blood counts. However, neointima development following wire injury of the carotid artery was significantly decreased in NLRP3-deficient mice as compared to wild-type controls. In all, NLRP3 plays a non-redundant role in vascular damage mediated neointima formation. Our data establish NLRP3 as a key player in the response to vascular damage, which could open new avenues to therapeutic intervention.

Performance Analysis of Cluster Formation in Wireless Sensor Networks.

Science.gov (United States)

Montiel, Edgar Romo; Rivero-Angeles, Mario E; Rubino, Gerardo; Molina-Lozano, Heron; Menchaca-Mendez, Rolando; Menchaca-Mendez, Ricardo

2017-12-13

Clustered-based wireless sensor networks have been extensively used in the literature in order to achieve considerable energy consumption reductions. However, two aspects of such systems have been largely overlooked. Namely, the transmission probability used during the cluster formation phase and the way in which cluster heads are selected. Both of these issues have an important impact on the performance of the system. For the former, it is common to consider that sensor nodes in a clustered-based Wireless Sensor Network (WSN) use a fixed transmission probability to send control data in order to build the clusters. However, due to the highly variable conditions experienced by these networks, a fixed transmission probability may lead to extra energy consumption. In view of this, three different transmission probability strategies are studied: optimal, fixed and adaptive. In this context, we also investigate cluster head selection schemes, specifically, we consider two intelligent schemes based on the fuzzy C-means and k-medoids algorithms and a random selection with no intelligence. We show that the use of intelligent schemes greatly improves the performance of the system, but their use entails higher complexity and selection delay. The main performance metrics considered in this work are energy consumption, successful transmission probability and cluster formation latency. As an additional feature of this work, we study the effect of errors in the wireless channel and the impact on the performance of the system under the different transmission probability schemes.

Performance Analysis of Cluster Formation in Wireless Sensor Networks

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Edgar Romo Montiel

2017-12-01

Full Text Available Clustered-based wireless sensor networks have been extensively used in the literature in order to achieve considerable energy consumption reductions. However, two aspects of such systems have been largely overlooked. Namely, the transmission probability used during the cluster formation phase and the way in which cluster heads are selected. Both of these issues have an important impact on the performance of the system. For the former, it is common to consider that sensor nodes in a clustered-based Wireless Sensor Network (WSN use a fixed transmission probability to send control data in order to build the clusters. However, due to the highly variable conditions experienced by these networks, a fixed transmission probability may lead to extra energy consumption. In view of this, three different transmission probability strategies are studied: optimal, fixed and adaptive. In this context, we also investigate cluster head selection schemes, specifically, we consider two intelligent schemes based on the fuzzy C-means and k-medoids algorithms and a random selection with no intelligence. We show that the use of intelligent schemes greatly improves the performance of the system, but their use entails higher complexity and selection delay. The main performance metrics considered in this work are energy consumption, successful transmission probability and cluster formation latency. As an additional feature of this work, we study the effect of errors in the wireless channel and the impact on the performance of the system under the different transmission probability schemes.

Effect of in situ hypothermic perfusion on intrahepatic pO(2) and reactive oxygen species formation after partial hepatectomy under total hepatic vascular exclusion in pigs

NARCIS (Netherlands)

Heijnen, Bob H. M.; Straatsburg, Irene H.; Kager, Liesbeth M.; van der Kleij, Ad J.; Gouma, Dirk J.; van Gulik, Thomas M.

2003-01-01

Aim: This study examined attenuation of ischemia and reperfusion (I/R) induced liver injury during liver resections by hypothermic perfusion of the liver under total hepatic vascular exclusion (THVE). Method: Reactive oxygen species (ROS) formation, microcirculatory integrity and endothelial cell

Vascular anatomy of the pig kidney glomerulus: a qualitative study of corrosion casts.

Science.gov (United States)

Moore, B J; Holmes, K R; Xu, L X

1992-09-01

Pig kidney glomerular vascular anatomy was studied by scanning electron microscopy of vascular corrosion casts. A generalized vascular architecture is presented to describe the pig kidney glomerulus based upon the observation of 3,800 vascular cast glomeruli. The relative simplicity of the pig glomerular vascular architecture has allowed the characterization of different vascular segments more completely than has been possible in other mammals. Based upon relationships to the afferent arteriole, a nomenclature and definition of primary, secondary, tertiary and anastomotic vessels is proposed for the distributing vessels comprising the glomerular tuft. The existence and formation of a large central hemispheric vessel deep within the confines of a glomerular hemisphere is micrographically documented. Micrographic evidence is presented supporting the formation of the single efferent arteriole by the merging of two central hemispheric vessels within the confines of the glomerular tuft. Failure of the merging of these two vessels may result in multiple efferent arterioles.

The hematopoietic chemokine CXCL12 promotes integration of human endothelial colony forming cell-derived cells into immature vessel networks.

Science.gov (United States)

Newey, Sarah E; Tsaknakis, Grigorios; Khoo, Cheen P; Athanassopoulos, Thanassi; Camicia, Rosalba; Zhang, Youyi; Grabowska, Rita; Harris, Adrian L; Roubelakis, Maria G; Watt, Suzanne M

2014-11-15

Proangiogenic factors, vascular endothelial growth factor (VEGF), and fibroblast growth factor-2 (FGF-2) prime endothelial cells to respond to "hematopoietic" chemokines and cytokines by inducing/upregulating expression of the respective chemokine/cytokine receptors. Coculture of human endothelial colony forming cell (ECFC)-derived cells with human stromal cells in the presence of VEGF and FGF-2 for 14 days resulted in upregulation of the "hematopoietic" chemokine CXCL12 and its CXCR4 receptor by day 3 of coculture. Chronic exposure to the CXCR4 antagonist AMD3100 in this vasculo/angiogenesis assay significantly reduced vascular tubule formation, an observation recapitulated by delayed AMD3100 addition. While AMD3100 did not affect ECFC-derived cell proliferation, it did demonstrate a dual action. First, over the later stages of the 14-day cocultures, AMD3100 delayed tubule organization into maturing vessel networks, resulting in enhanced endothelial cell retraction and loss of complexity as defined by live cell imaging. Second, at earlier stages of cocultures, we observed that AMD3100 significantly inhibited the integration of exogenous ECFC-derived cells into established, but immature, vascular networks. Comparative proteome profiler array analyses of ECFC-derived cells treated with AMD3100 identified changes in expression of potential candidate molecules involved in adhesion and/or migration. Blocking antibodies to CD31, but not CD146 or CD166, reduced the ECFC-derived cell integration into these extant vascular networks. Thus, CXCL12 plays a key role not only in endothelial cell sensing and guidance, but also in promoting the integration of ECFC-derived cells into developing vascular networks.

Angiología y cirugía vascular en la formación del médico general básico Angiology and vascular surgery in the formation of the basic comprehensive doctor

Directory of Open Access Journals (Sweden)

Gladys Rojas Reyes

2007-09-01

Full Text Available Los estudios epidemiológicos sobre las afecciones vasculares periféricas han demostrado que ocupan un lugar significativo en la morbilidad y mortalidad de la población adulta. Por lo tanto se hace necesario que el Médico General Básico, con el dominio de los conocimientos pertinentes para su formación pueda realizar la profilaxis, el diagnóstico precoz y la conducta a seguir en la comunidad de toda esta gama de afecciones vasculares. Dentro de estas patologías se encuentra incluido el llamado Pie diabético, de alta morbilidad y mortalidad, el cual no figura en el actual plan de estudio de Medicina. Por lo que los autores en el presente trabajo pretendieron realizar una propuesta donde quede incluida dicha entidad, para una correcta dirección del proceso docente educativo en la formación de este nuevo modelo, a partir de la universalización de la carrera de medicina y la nueva concepción de formación de los recursos humanos en el escenario docente de excelencia: el Policlínico Universitario, jugando un papel activo el estudiante como constructor de su conocimiento.Epidemiological studies on peripheral vascular disorders have showed them to have a significant place in morbidity and mortality rate in adults. Therefore, it is necessary for the basic comprehensive doctor, with mastering of the pertinent knowledge for his formation, to be able to perform prophylaxis, early diagnosis and behaviour in the community of all the group of vascular disorders. These pathologies include the so called diabetic foot, with a high morbidity and mortality rate, which is not included in the current syllabus of Medicine. Therefore the authors of this paper made a proposal so that this entity will be included for a correct direction of the educational teaching process in the creation of this new model. From the universalization of the Medicine major and the new conception of formation of human resources in the teaching scenario of excellence: University

Albendazole inhibits endothelial cell migration, tube formation, vasopermeability, VEGF receptor-2 expression and suppresses retinal neovascularization in ROP model of angiogenesis

Energy Technology Data Exchange (ETDEWEB)

Pourgholami, Mohammad H., E-mail: mh.pourgholami@unsw.edu.au [University of New South Wales, Department of Surgery, St George Hospital (SESIAHS), Sydney (Australia); Khachigian, Levon M.; Fahmy, Roger G. [Centre for Vascular Research, The University of New South Wales, Department of Haematology, The Prince of Wales Hospital, Sydney (Australia); Badar, Samina; Wang, Lisa; Chu, Stephanie Wai Ling; Morris, David Lawson [University of New South Wales, Department of Surgery, St George Hospital (SESIAHS), Sydney (Australia)

2010-07-09

The angiogenic process begins with the cell proliferation and migration into the primary vascular network, and leads to vascularization of previously avascular tissues and organs as well to growth and remodeling of the initially homogeneous capillary plexus to form a new microcirculation. Additionally, an increase in microvascular permeability is a crucial step in angiogenesis. Vascular endothelial growth factor (VEGF) plays a central role in angiogenesis. We have previously reported that albendazole suppresses VEGF levels and inhibits malignant ascites formation, suggesting a possible effect on angiogenesis. This study was therefore designed to investigate the antiangiogenic effect of albendazole in non-cancerous models of angiogenesis. In vitro, treatment of human umbilical vein endothelial cells (HUVECs) with albendazole led to inhibition of tube formation, migration, permeability and down-regulation of the VEGF type 2 receptor (VEGFR-2). In vivo albendazole profoundly inhibited hyperoxia-induced retinal angiogenesis in mice. These results provide new insights into the antiangiogenic effects of albendazole.

Albendazole inhibits endothelial cell migration, tube formation, vasopermeability, VEGF receptor-2 expression and suppresses retinal neovascularization in ROP model of angiogenesis

International Nuclear Information System (INIS)

Pourgholami, Mohammad H.; Khachigian, Levon M.; Fahmy, Roger G.; Badar, Samina; Wang, Lisa; Chu, Stephanie Wai Ling; Morris, David Lawson

2010-01-01

The angiogenic process begins with the cell proliferation and migration into the primary vascular network, and leads to vascularization of previously avascular tissues and organs as well to growth and remodeling of the initially homogeneous capillary plexus to form a new microcirculation. Additionally, an increase in microvascular permeability is a crucial step in angiogenesis. Vascular endothelial growth factor (VEGF) plays a central role in angiogenesis. We have previously reported that albendazole suppresses VEGF levels and inhibits malignant ascites formation, suggesting a possible effect on angiogenesis. This study was therefore designed to investigate the antiangiogenic effect of albendazole in non-cancerous models of angiogenesis. In vitro, treatment of human umbilical vein endothelial cells (HUVECs) with albendazole led to inhibition of tube formation, migration, permeability and down-regulation of the VEGF type 2 receptor (VEGFR-2). In vivo albendazole profoundly inhibited hyperoxia-induced retinal angiogenesis in mice. These results provide new insights into the antiangiogenic effects of albendazole.

The development of a reflective vascular training portfolio: Using a ...

African Journals Online (AJOL)

... of formative assessment to certify candidates. Case-based self-reflection in postgraduate training may be used as an additional educational tool and incorporated into the curricula vitae of trainees. We describe the method used to assess a vascular case, based on a self-reflective training method (vascular case portfolio).

Dynamics of blood flow and thrombus formation in a multi-bypass microfluidic ladder network.

Science.gov (United States)

Zilberman-Rudenko, Jevgenia; Sylman, Joanna L; Lakshmanan, Hari H S; McCarty, Owen J T; Maddala, Jeevan

2017-02-01

The reaction dynamics of a complex mixture of cells and proteins, such as blood, in branched circulatory networks within the human microvasculature or extravascular therapeutic devices such as extracorporeal oxygenation machine (ECMO) remains ill-defined. In this report we utilize a multi-bypass microfluidics ladder network design with dimensions mimicking venules to study patterns of blood platelet aggregation and fibrin formation under complex shear. Complex blood fluid dynamics within multi-bypass networks under flow were modeled using COMSOL. Red blood cells and platelets were assumed to be non-interacting spherical particles transported by the bulk fluid flow, and convection of the activated coagulation factor II, thrombin, was assumed to be governed by mass transfer. This model served as the basis for predicting formation of local shear rate gradients, stagnation points and recirculation zones as dictated by the bypass geometry. Based on the insights from these models, we were able to predict the patterns of blood clot formation at specific locations in the device. Our experimental data was then used to adjust the model to account for the dynamical presence of thrombus formation in the biorheology of blood flow. The model predictions were then compared to results from experiments using recalcified whole human blood. Microfluidic devices were coated with the extracellular matrix protein, fibrillar collagen, and the initiator of the extrinsic pathway of coagulation, tissue factor. Blood was perfused through the devices at a flow rate of 2 µL/min, translating to physiologically relevant initial shear rates of 300 and 700 s -1 for main channels and bypasses, respectively. Using fluorescent and light microscopy, we observed distinct flow and thrombus formation patterns near channel intersections at bypass points, within recirculation zones and at stagnation points. Findings from this proof-of-principle ladder network model suggest a specific correlation between

Sustained Angiopoietin-2 Expression Disrupts Vessel Formation and Inhibits Glioma Growth

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Ok-Hee Lee

2006-05-01

Full Text Available Systematic analyses of the expression of angiogenic regulators in cancer models should yield useful information for the development of novel therapies for malignant gliomas. In this study, we analyzed tumor growth, vascularization, and angiopoietin-2 (Ang2 expression during the development of U-87 MG xenografts. We found that tumoral angiogenesis in this model follows a multistage process characterized by avascular, prolific peripheral angiogenesis, and late vascular phases. On day 4, we observed an area of central necrosis, a peripheral ring of Ang2-positive glioma cells, and reactive Ang2-positive vascular structures in the tumor/brain interface. When the tumor had developed a vascular network, Ang2 was expressed only in peripheral vascular structures. Because Ang2 expression was downmodulated in the late stages of development, probably to maintain a stable tumoral vasculature, we next studied whether sustained Ang2 expression might impair vascular development and, ultimately, tumor growth. Ang2 prevented the formation of capillary-like structures and impaired angiogenesis in a chorioallantoic membrane chicken model. Finally, we tested the effect of sustained Ang2 expression on U-87 MG xenograff development. Ang2 significantly prolonged the survival of intracranial U-87 MG tumor-bearing animals. Examination of Ang2treated xenograffs revealed areas of tumor necrosis and vascular damage. We therefore conclude that deregulated Ang2 expression during gliomagenesis hindered successful angiogenesis and that therapies that sustain Ang2 expression might be effective against malignant gliomas.

Vascular Gene Expression: A Hypothesis

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Angélica Concepción eMartínez-Navarro

2013-07-01

Full Text Available The phloem is the conduit through which photoassimilates are distributed from autotrophic to heterotrophic tissues and is involved in the distribution of signaling molecules that coordinate plant growth and responses to the environment. Phloem function depends on the coordinate expression of a large array of genes. We have previously identified conserved motifs in upstream regions of the Arabidopsis genes, encoding the homologs of pumpkin phloem sap mRNAs, displaying expression in vascular tissues. This tissue-specific expression in Arabidopsis is predicted by the overrepresentation of GA/CT-rich motifs in gene promoters. In this work we have searched for common motifs in upstream regions of the homologous genes from plants considered to possess a primitive vascular tissue (a lycophyte, as well as from others that lack a true vascular tissue (a bryophyte, and finally from chlorophytes. Both lycophyte and bryophyte display motifs similar to those found in Arabidopsis with a significantly low E-value, while the chlorophytes showed either a different conserved motif or no conserved motif at all. These results suggest that these same genes are expressed coordinately in non- vascular plants; this coordinate expression may have been one of the prerequisites for the development of conducting tissues in plants. We have also analyzed the phylogeny of conserved proteins that may be involved in phloem function and development. The presence of CmPP16, APL, FT and YDA in chlorophytes suggests the recruitment of ancient regulatory networks for the development of the vascular tissue during evolution while OPS is a novel protein specific to vascular plants.

TLR accessory molecule RP105 (CD180 is involved in post-interventional vascular remodeling and soluble RP105 modulates neointima formation.

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Jacco C Karper

Full Text Available BACKGROUND: RP105 (CD180 is TLR4 homologue lacking the intracellular TLR4 signaling domain and acts a TLR accessory molecule and physiological inhibitor of TLR4-signaling. The role of RP105 in vascular remodeling, in particular post-interventional remodeling is unknown. METHODS AND RESULTS: TLR4 and RP105 are expressed on vascular smooth muscle cells (VSMC as well as in the media of murine femoral artery segments as detected by qPCR and immunohistochemistry. Furthermore, the response to the TLR4 ligand LPS was stronger in VSMC from RP105(-/- mice resulting in a higher proliferation rate. In RP105(-/- mice femoral artery cuff placement resulted in an increase in neointima formation as compared to WT mice (4982 ± 974 µm(2 vs.1947 ± 278 µm(2,p = 0.0014. Local LPS application augmented neointima formation in both groups, but in RP105(-/- mice this effect was more pronounced (10316±1243 µm(2 vs.4208 ± 555 µm(2,p = 0.0002, suggesting a functional role for RP105. For additional functional studies, the extracellular domain of murine RP105 was expressed with or without its adaptor protein MD1 and purified. SEC-MALSanalysis showed a functional 2∶2 homodimer formation of the RP105-MD1 complex. This protein complex was able to block the TLR4 response in whole blood ex-vivo. In vivo gene transfer of plasmid vectors encoding the extracellular part of RP105 and its adaptor protein MD1 were performed to initiate a stable endogenous soluble protein production. Expression of soluble RP105-MD1 resulted in a significant reduction in neointima formation in hypercholesterolemic mice (2500 ± 573 vs.6581 ± 1894 µm(2,p<0.05, whereas expression of the single factors RP105 or MD1 had no effect. CONCLUSION: RP105 is a potent inhibitor of post-interventional neointima formation.

FGF-dependent metabolic control of vascular development

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Yu, Pengchun; Alves, Tiago C.; Fang, Jennifer S.; Xie, Yi; Zhu, Jie; Chen, Zehua; De Smet, Frederik; Zhang, Jiasheng; Jin, Suk-Won; Sun, Lele; Sun, Hongye; Kibbey, Richard G.; Hirschi, Karen K.; Hay, Nissim; Carmeliet, Peter; Chittenden, Thomas W.; Eichmann, Anne; Potente, Michael; Simons, Michael

2017-01-01

Blood and lymphatic vasculatures are intimately involved in tissue oxygenation and fluid homeostasis maintenance. Assembly of these vascular networks involves sprouting, migration and proliferation of endothelial cells. Recent studies have suggested that changes in cellular metabolism are of importance to these processes1. While much is known about vascular endothelial growth factor (VEGF)-dependent regulation of vascular development and metabolism2,3, little is understood about the role of fibroblast growth factors (FGFs) in this context4. Here we identify FGF receptor (FGFR) signaling as a critical regulator of vascular development. This is achieved by FGF-dependent control of c-MYC (MYC) expression that, in turn, regulates expression of the glycolytic enzyme hexokinase 2 (HK2). A decrease in HK2 levels in the absence of FGF signaling inputs results in decreased glycolysis leading to impaired endothelial cell proliferation and migration. Pan-endothelial- and lymphatic-specific Hk2 knockouts phenocopy blood and/or lymphatic vascular defects seen in Fgfr1/r3 double mutant mice while HK2 overexpression partially rescues the defects caused by suppression of FGF signaling. Thus, FGF-dependent regulation of endothelial glycolysis is a pivotal process in developmental and adult vascular growth and development. PMID:28467822

Motif formation and industry specific topologies in the Japanese business firm network

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Maluck, Julian; Donner, Reik V.; Takayasu, Hideki; Takayasu, Misako

2017-05-01

Motifs and roles are basic quantities for the characterization of interactions among 3-node subsets in complex networks. In this work, we investigate how the distribution of 3-node motifs can be influenced by modifying the rules of an evolving network model while keeping the statistics of simpler network characteristics, such as the link density and the degree distribution, invariant. We exemplify this problem for the special case of the Japanese Business Firm Network, where a well-studied and relatively simple yet realistic evolving network model is available, and compare the resulting motif distribution in the real-world and simulated networks. To better approximate the motif distribution of the real-world network in the model, we introduce both subgraph dependent and global additional rules. We find that a specific rule that allows only for the merging process between nodes with similar link directionality patterns reduces the observed excess of densely connected motifs with bidirectional links. Our study improves the mechanistic understanding of motif formation in evolving network models to better describe the characteristic features of real-world networks with a scale-free topology.

Investigating water transport through the xylem network in vascular plants.

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Kim, Hae Koo; Park, Joonghyuk; Hwang, Ildoo

2014-04-01

Our understanding of physical and physiological mechanisms depends on the development of advanced technologies and tools to prove or re-evaluate established theories, and test new hypotheses. Water flow in land plants is a fascinating phenomenon, a vital component of the water cycle, and essential for life on Earth. The cohesion-tension theory (CTT), formulated more than a century ago and based on the physical properties of water, laid the foundation for our understanding of water transport in vascular plants. Numerous experimental tools have since been developed to evaluate various aspects of the CTT, such as the existence of negative hydrostatic pressure. This review focuses on the evolution of the experimental methods used to study water transport in plants, and summarizes the different ways to investigate the diversity of the xylem network structure and sap flow dynamics in various species. As water transport is documented at different scales, from the level of single conduits to entire plants, it is critical that new results be subjected to systematic cross-validation and that findings based on different organs be integrated at the whole-plant level. We also discuss the functional trade-offs between optimizing hydraulic efficiency and maintaining the safety of the entire transport system. Furthermore, we evaluate future directions in sap flow research and highlight the importance of integrating the combined effects of various levels of hydraulic regulation.

Strategies in interventional radiology. Formation of an interdisciplinary center of vascular anomalies. Chances and challenges for effective and efficient patient management; Strategien in der interventionellen Radiologie. Gruendung eines Interdisziplinaeres Zentrum fuer Gefaessanomalien. Chancen und Herausforderungen fuer effektives und effizientes Patientenmanagement

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Sadick, Maliha; Dally, Franz Josef; Schoenberg, Stefan O. [University Medical Center Mannheim (Germany). Interdisciplinary Center for Vascular Anomalies; Stroszczynski, Christian [University Hospital Regensburg (Germany). Dept. of Radiology; Wohlgemuth, Walter A. [University Hospital Halle (Germany). Interdisciplinary Center for Vascular Anomalies

2017-10-15

Radiology is an interdisciplinary field dedicated to the diagnosis and treatment of numerous diseases and is involved in the development of multimodal treatment concepts. Interdisciplinary case management, a broad spectrum of diagnostic imaging facilities and dedicated endovascular radiological treatment options are valuable tools that allow radiology to set up an interdisciplinary center for vascular anomalies. Image-based diagnosis combined with endovascular treatment options is an essential tool for the treatment of patients with highly complex vascular diseases. These vascular anomalies can affect numerous parts of the body so that a multidisciplinary treatment approach is required for optimal patient care. This paper discusses the possibilities and challenges regarding effective and efficient patient management in connection with the formation of an interdisciplinary center for vascular anomalies with strengthening of the clinical role of radiologists. Key points: Vascular anomalies, which include vascular tumors and malformations, are complex to diagnose and treat. There are far more patients with vascular anomalies requiring therapy than interdisciplinary centers for vascular anomalies - there is currently a shortage of dedicated interdisciplinary centers for vascular anomalies in Germany that can provide dedicated care for affected patients. Radiology includes a broad spectrum of diagnostic and minimally invasive therapeutic tools which allow the formation of an interdisciplinary center for vascular anomalies for effective, efficient and comprehensive patient management.

Analysis of the packet formation process in packet-switched networks

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Meditch, J. S.

Two new queueing system models for the packet formation process in packet-switched telecommunication networks are developed, and their applications in process stability, performance analysis, and optimization studies are illustrated. The first, an M/M/1 queueing system characterization of the process, is a highly aggregated model which is useful for preliminary studies. The second, a marked extension of an earlier M/G/1 model, permits one to investigate stability, performance characteristics, and design of the packet formation process in terms of the details of processor architecture, and hardware and software implementations with processor structure and as many parameters as desired as variables. The two new models together with the earlier M/G/1 characterization span the spectrum of modeling complexity for the packet formation process from basic to advanced.

Experimental study upon the effect of irradiation on callus formation of fracture

International Nuclear Information System (INIS)

Saigusa, Fujio

1981-01-01

Irradiation effects on callus formation after bone fracture were studied in rats with fractured right lower extremity. Follow-up study was continued for 112 days since 3000 rad was irradiated to the fractured site 3 days after bone fracture. Callus formation was noted in both of the outer and inner part (bone marrow) of the diaphysis before 14 days after bone fracture, but it was slow and sparse compared with that of non-irradiated group. Callus formation tended to disappear gradually from the outside of the diaphysis after 28 days after bone fracture. Strong disturbance was found in the surrounding vascular system at this time. Inside of the diaphysis, callus formation was restricted the end of the fracture, where lamellar calluses fused together. Changes in vascular system remained until 56 days after bone fracture. Vascular distribution was most dense 28 days after bone fracture. In many of the calluses which have established fusion, findings suggested excessive calcification in the trabeculae. Vascular distribution at this time was sparse, vascular formation was markedly suppressed in the bone marrow, and very little vascular formation was found in the fractured edges of the bone. (Ueda, J.)

Vascular Complications of Pancreatitis: Role of Interventional Therapy

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Barge, Jaideep U.; Lopera, Jorge E. [University of Texas Health Science Center, San Antonio (United States)

2012-02-15

Major vascular complications related to pancreatitis can cause life-threatening hemorrhage and have to be dealt with as an emergency, utilizing a multidisciplinary approach of angiography, endoscopy or surgery. These may occur secondary to direct vascular injuries, which result in the formation of splanchnic pseudoaneurysms, gastrointestinal etiologies such as peptic ulcer disease and gastroesophageal varices, and post-operative bleeding related to pancreatic surgery. In this review article, we discuss the pathophysiologic mechanisms, diagnostic modalities, and treatment of pancreatic vascular complications, with a focus on the role of minimally-invasive interventional therapies such as angioembolization, endovascular stenting, and ultrasound-guided percutaneous thrombin injection in their management.

Differentiation and Application of Induced Pluripotent Stem Cell-Derived Vascular Smooth Muscle Cells.

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Maguire, Eithne Margaret; Xiao, Qingzhong; Xu, Qingbo

2017-11-01

Vascular smooth muscle cells (VSMCs) play a role in the development of vascular disease, for example, neointimal formation, arterial aneurysm, and Marfan syndrome caused by genetic mutations in VSMCs, but little is known about the mechanisms of the disease process. Advances in induced pluripotent stem cell technology have now made it possible to derive VSMCs from several different somatic cells using a selection of protocols. As such, researchers have set out to delineate key signaling processes involved in triggering VSMC gene expression to grasp the extent of gene regulatory networks involved in phenotype commitment. This technology has also paved the way for investigations into diseases affecting VSMC behavior and function, which may be treatable once an identifiable culprit molecule or gene has been repaired. Moreover, induced pluripotent stem cell-derived VSMCs are also being considered for their use in tissue-engineered blood vessels as they may prove more beneficial than using autologous vessels. Finally, while several issues remains to be clarified before induced pluripotent stem cell-derived VSMCs can become used in regenerative medicine, they do offer both clinicians and researchers hope for both treating and understanding vascular disease. In this review, we aim to update the recent progress on VSMC generation from stem cells and the underlying molecular mechanisms of VSMC differentiation. We will also explore how the use of induced pluripotent stem cell-derived VSMCs has changed the game for regenerative medicine by offering new therapeutic avenues to clinicians, as well as providing researchers with a new platform for modeling of vascular disease. © 2017 American Heart Association, Inc.

The role of endogenous and exogenous mechanisms in the formation of R&D networks

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Tomasello, Mario V.; Perra, Nicola; Tessone, Claudio J.; Karsai, Márton; Schweitzer, Frank

2014-01-01

We develop an agent-based model of strategic link formation in Research and Development (R&D) networks. Empirical evidence has shown that the growth of these networks is driven by mechanisms which are both endogenous to the system (that is, depending on existing alliances patterns) and exogenous (that is, driven by an exploratory search for newcomer firms). Extant research to date has not investigated both mechanisms simultaneously in a comparative manner. To overcome this limitation, we develop a general modeling framework to shed light on the relative importance of these two mechanisms. We test our model against a comprehensive dataset, listing cross-country and cross-sectoral R&D alliances from 1984 to 2009. Our results show that by fitting only three macroscopic properties of the network topology, this framework is able to reproduce a number of micro-level measures, including the distributions of degree, local clustering, path length and component size, and the emergence of network clusters. Furthermore, by estimating the link probabilities towards newcomers and established firms from the data, we find that endogenous mechanisms are predominant over the exogenous ones in the network formation, thus quantifying the importance of existing structures in selecting partner firms. PMID:25022561

The role of endogenous and exogenous mechanisms in the formation of R&D networks

Science.gov (United States)

Tomasello, Mario V.; Perra, Nicola; Tessone, Claudio J.; Karsai, Márton; Schweitzer, Frank

2014-07-01

We develop an agent-based model of strategic link formation in Research and Development (R&D) networks. Empirical evidence has shown that the growth of these networks is driven by mechanisms which are both endogenous to the system (that is, depending on existing alliances patterns) and exogenous (that is, driven by an exploratory search for newcomer firms). Extant research to date has not investigated both mechanisms simultaneously in a comparative manner. To overcome this limitation, we develop a general modeling framework to shed light on the relative importance of these two mechanisms. We test our model against a comprehensive dataset, listing cross-country and cross-sectoral R&D alliances from 1984 to 2009. Our results show that by fitting only three macroscopic properties of the network topology, this framework is able to reproduce a number of micro-level measures, including the distributions of degree, local clustering, path length and component size, and the emergence of network clusters. Furthermore, by estimating the link probabilities towards newcomers and established firms from the data, we find that endogenous mechanisms are predominant over the exogenous ones in the network formation, thus quantifying the importance of existing structures in selecting partner firms.

Experimental Branch Retinal Vein Occlusion Induces Upstream Pericyte Loss and Vascular Destabilization.

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Elisa Dominguez

Full Text Available Branch retinal vein occlusion (BRVO leads to extensive vascular remodeling and is important cause of visual impairment. Although the vascular morphological changes following experimental vein occlusion have been described in a variety of models using angiography, the underlying cellular events are ill defined.We here show that laser-induced experimental BRVO in mice leads to a wave of TUNEL-positive endothelial cell (EC apoptosis in the upstream vascular network associated with a transient edema and hemorrhages. Subsequently, we observe an induction of EC proliferation within the dilated vein and capillaries, detected by EdU incorporation, and the edema resolves. However, the pericytes of the upstream capillaries are severely reduced, which was associated with continuing EC apoptosis and proliferation. The vascular remodeling was associated with increased expression of TGFβ, TSP-1, but also FGF2 expression. Exposure of the experimental animals to hypoxia, when pericyte (PC dropout had occurred, led to a dramatic increase in endothelial cell proliferation, confirming the vascular instability induced by the experimental BRVO.Experimental BRVO leads to acute endothelial cells apoptosis and increased permeability. Subsequently the upstream vascular network remains destabilized, characterized by pericyte dropout, un-physiologically high endothelial cells turnover and sensitivity to hypoxia. These early changes might pave the way for capillary loss and subsequent chronic ischemia and edema that characterize the late stage disease.

Robust Drones Formation Control in 5G Wireless Sensor Network Using mmWave

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Shan Meng

2018-01-01

Full Text Available The drones formation control in 5G wireless sensor network is discussed. The base station (BS is used to receive backhaul position signals from the lead drone in formation and launches the beam to the lead one as the fronthaul flying signal enhancement. It is a promising approach to raise the formation strength of drones during flight control. The BS can transform the direction of the antennas and transmit energy to the lead drone that could widely enlarge the number of the receivers and increase the transmission speed of the data links. The millimeter-Wave (mmWave communication system offers new opportunities to meet this requirement owing to the tremendous amount of available spectrums. However, the massive non-line-of-sight (NLoS transmission and the site constraints in urban environment are severely challenging the conventional deploying terrestrial low power nodes (LPNs. Simulation experiments have been performed to verify the availability and effectiveness of mmWave in 5G wireless sensor network.

Diagnostic dilemma in vascular mal-formation of the upper lip: a ...

African Journals Online (AJOL)

richard

2014-09-08

Sep 8, 2014 ... Radiography, Lagos University Teaching Hospital, Lagos. *Corresponding author: ... To present a case of vascular lesion on the upper lip and its management. Methods: We .... midline of the face without bone involvement.

Acceleration of vascularized bone tissue-engineered constructs in a large animal model combining intrinsic and extrinsic vascularization.

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Weigand, Annika; Beier, Justus P; Hess, Andreas; Gerber, Thomas; Arkudas, Andreas; Horch, Raymund E; Boos, Anja M

2015-05-01

During the last decades, a range of excellent and promising strategies in Bone Tissue Engineering have been developed. However, the remaining major problem is the lack of vascularization. In this study, extrinsic and intrinsic vascularization strategies were combined for acceleration of vascularization. For optimal biomechanical stability of the defect site and simplifying future transition into clinical application, a primary stable and approved nanostructured bone substitute in clinically relevant size was used. An arteriovenous (AV) loop was microsurgically created in sheep and implanted, together with the bone substitute, in either perforated titanium chambers (intrinsic/extrinsic) for different time intervals of up to 18 weeks or isolated Teflon(®) chambers (intrinsic) for 18 weeks. Over time, magnetic resonance imaging and micro-computed tomography (CT) analyses illustrate the dense vascularization arising from the AV loop. The bone substitute was completely interspersed with newly formed tissue after 12 weeks of intrinsic/extrinsic vascularization and after 18 weeks of intrinsic/extrinsic and intrinsic vascularization. Successful matrix change from an inorganic to an organic scaffold could be demonstrated in vascularized areas with scanning electron microscopy and energy dispersive X-ray spectroscopy. Using the intrinsic vascularization method only, the degradation of the scaffold and osteoclastic activity was significantly lower after 18 weeks, compared with 12 and 18 weeks in the combined intrinsic-extrinsic model. Immunohistochemical staining revealed an increase in bone tissue formation over time, without a difference between intrinsic/extrinsic and intrinsic vascularization after 18 weeks. This study presents the combination of extrinsic and intrinsic vascularization strategies for the generation of an axially vascularized bone substitute in clinically relevant size using a large animal model. The additional extrinsic vascularization promotes tissue

The impact of KRAS mutations on VEGF-A production and tumour vascular network

International Nuclear Information System (INIS)

Figueras, Agnès; Arbos, Maria Antonia; Quiles, Maria Teresa; Viñals, Francesc; Germà, Josep Ramón; Capellà, Gabriel

2013-01-01

The malignant potential of tumour cells may be influenced by the molecular nature of KRAS mutations being codon 13 mutations less aggressive than codon 12 ones. Their metabolic profile is also different, with an increased anaerobic glycolytic metabolism in cells harbouring codon 12 KRAS mutations compared with cells containing codon 13 mutations. We hypothesized that this distinct metabolic behaviour could be associated with different HIF-1α expression and a distinct angiogenic profile. Codon13 KRAS mutation (ASP13) or codon12 KRAS mutation (CYS12) NIH3T3 transfectants were analyzed in vitro and in vivo. Expression of HIF-1α, and VEGF-A was studied at RNA and protein levels. Regulation of VEGF-A promoter activity was assessed by means of luciferase assays using different plasmid constructs. Vascular network was assessed in tumors growing after subcutaneous inoculation. Non parametric statistics were used for analysis of results. Our results show that in normoxic conditions ASP13 transfectants exhibited less HIF-1α protein levels and activity than CYS12. In contrast, codon 13 transfectants exhibited higher VEGF-A mRNA and protein levels and enhanced VEGF-A promoter activity. These differences were due to a differential activation of Sp1/AP2 transcription elements of the VEGF-A promoter associated with increased ERKs signalling in ASP13 transfectants. Subcutaneous CYS12 tumours expressed less VEGF-A and showed a higher microvessel density (MVD) than ASP13 tumours. In contrast, prominent vessels were only observed in the latter. Subtle changes in the molecular nature of KRAS oncogene activating mutations occurring in tumour cells have a major impact on the vascular strategy devised providing with new insights on the role of KRAS mutations on angiogenesis

Vinpocetine Attenuates the Osteoblastic Differentiation of Vascular Smooth Muscle Cells.

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Yun-Yun Ma

Full Text Available Vascular calcification is an active process of osteoblastic differentiation of vascular smooth muscle cells; however, its definite mechanism remains unknown. Vinpocetine, a derivative of the alkaloid vincamine, has been demonstrated to inhibit the high glucose-induced proliferation of vascular smooth muscle cells; however, it remains unknown whether vinpocetine can affect the osteoblastic differentiation of vascular smooth muscle cells. We hereby investigated the effect of vinpocetine on vascular calcification using a beta-glycerophosphate-induced cell model. Our results showed that vinpocetine significantly reduced the osteoblast-like phenotypes of vascular smooth muscle cells including ALP activity, osteocalcin, collagen type I, Runx2 and BMP-2 expression as well as the formation of mineralized nodule. Vinpocetine, binding to translocation protein, induced phosphorylation of extracellular signal-related kinase and Akt and thus inhibited the translocation of nuclear factor-kappa B into the nucleus. Silencing of translocator protein significantly attenuated the inhibitory effect of vinpocetine on osteoblastic differentiation of vascular smooth muscle cells. Taken together, vinpocetine may be a promising candidate for the clinical therapy of vascular calcification.

Tissue vascularization through 3D printing: Will technology bring us flow?

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Paulsen, S J; Miller, J S

2015-05-01

Though in vivo models provide the most physiologically relevant environment for studying tissue function, in vitro studies provide researchers with explicit control over experimental conditions and the potential to develop high throughput testing methods. In recent years, advancements in developmental biology research and imaging techniques have significantly improved our understanding of the processes involved in vascular development. However, the task of recreating the complex, multi-scale vasculature seen in in vivo systems remains elusive. 3D bioprinting offers a potential method to generate controlled vascular networks with hierarchical structure approaching that of in vivo networks. Bioprinting is an interdisciplinary field that relies on advances in 3D printing technology along with advances in imaging and computational modeling, which allow researchers to monitor cellular function and to better understand cellular environment within the printed tissue. As bioprinting technologies improve with regards to resolution, printing speed, available materials, and automation, 3D printing could be used to generate highly controlled vascularized tissues in a high throughput manner for use in regenerative medicine and the development of in vitro tissue models for research in developmental biology and vascular diseases. © 2015 Wiley Periodicals, Inc.

A quantitative theory of solid tumor growth, metabolic rate and vascularization.

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Alexander B Herman

Full Text Available The relationships between cellular, structural and dynamical properties of tumors have traditionally been studied separately. Here, we construct a quantitative, predictive theory of solid tumor growth, metabolic rate, vascularization and necrosis that integrates the relationships between these properties. To accomplish this, we develop a comprehensive theory that describes the interface and integration of the tumor vascular network and resource supply with the cardiovascular system of the host. Our theory enables a quantitative understanding of how cells, tissues, and vascular networks act together across multiple scales by building on recent theoretical advances in modeling both healthy vasculature and the detailed processes of angiogenesis and tumor growth. The theory explicitly relates tumor vascularization and growth to metabolic rate, and yields extensive predictions for tumor properties, including growth rates, metabolic rates, degree of necrosis, blood flow rates and vessel sizes. Besides these quantitative predictions, we explain how growth rates depend on capillary density and metabolic rate, and why similar tumors grow slower and occur less frequently in larger animals, shedding light on Peto's paradox. Various implications for potential therapeutic strategies and further research are discussed.

The vascular basement membrane in the healthy and pathological brain.

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Thomsen, Maj S; Routhe, Lisa J; Moos, Torben

2017-10-01

The vascular basement membrane contributes to the integrity of the blood-brain barrier (BBB), which is formed by brain capillary endothelial cells (BCECs). The BCECs receive support from pericytes embedded in the vascular basement membrane and from astrocyte endfeet. The vascular basement membrane forms a three-dimensional protein network predominantly composed of laminin, collagen IV, nidogen, and heparan sulfate proteoglycans that mutually support interactions between BCECs, pericytes, and astrocytes. Major changes in the molecular composition of the vascular basement membrane are observed in acute and chronic neuropathological settings. In the present review, we cover the significance of the vascular basement membrane in the healthy and pathological brain. In stroke, loss of BBB integrity is accompanied by upregulation of proteolytic enzymes and degradation of vascular basement membrane proteins. There is yet no causal relationship between expression or activity of matrix proteases and the degradation of vascular matrix proteins in vivo. In Alzheimer's disease, changes in the vascular basement membrane include accumulation of Aβ, composite changes, and thickening. The physical properties of the vascular basement membrane carry the potential of obstructing drug delivery to the brain, e.g. thickening of the basement membrane can affect drug delivery to the brain, especially the delivery of nanoparticles.

GDTN: Genome-Based Delay Tolerant Network Formation in Heterogeneous 5G Using Inter-UA Collaboration.

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You, Ilsun; Sharma, Vishal; Atiquzzaman, Mohammed; Choo, Kim-Kwang Raymond

2016-01-01

With a more Internet-savvy and sophisticated user base, there are more demands for interactive applications and services. However, it is a challenge for existing radio access networks (e.g. 3G and 4G) to cope with the increasingly demanding requirements such as higher data rates and wider coverage area. One potential solution is the inter-collaborative deployment of multiple radio devices in a 5G setting designed to meet exacting user demands, and facilitate the high data rate requirements in the underlying networks. These heterogeneous 5G networks can readily resolve the data rate and coverage challenges. Networks established using the hybridization of existing networks have diverse military and civilian applications. However, there are inherent limitations in such networks such as irregular breakdown, node failures, and halts during speed transmissions. In recent years, there have been attempts to integrate heterogeneous 5G networks with existing ad hoc networks to provide a robust solution for delay-tolerant transmissions in the form of packet switched networks. However, continuous connectivity is still required in these networks, in order to efficiently regulate the flow to allow the formation of a robust network. Therefore, in this paper, we present a novel network formation consisting of nodes from different network maneuvered by Unmanned Aircraft (UA). The proposed model utilizes the features of a biological aspect of genomes and forms a delay tolerant network with existing network models. This allows us to provide continuous and robust connectivity. We then demonstrate that the proposed network model has an efficient data delivery, lower overheads and lesser delays with high convergence rate in comparison to existing approaches, based on evaluations in both real-time testbed and simulation environment.

Vascular neurology nurse practitioner provision of telemedicine consultations.

Science.gov (United States)

Demaerschalk, Bart M; Kiernan, Terri-Ellen J; Investigators, Starr

2010-01-01

Objective. The objective was to define and evaluate a role for the Vascular Neurology-Nurse Practitioner (VN-NP) in the delivery of telemedicine consultations in partnership with a vascular neurologist. Methods. Prospective stroke alert patients at participating hospitals underwent a two-way audio video telemedicine consultation with a VN-NP at a remotely located stroke center in partnership with a vascular neurologist. Demographic information, National Institutes of Health Stroke Scale (NIHSS) scores, diagnoses, CT contraindications to thrombolysis, thrombolysis eligibility, and time interval data were collected. The inter-rater agreement between VN-NP and vascular neurologist assessments was calculated. Results. Ten patients were evaluated. Four were determined to have ischemic stroke, one had a transient ischemic attack, two had intracerebral hemorrhages, and three were stroke mimics. Overall, three patients received thrombolysis. The inter-rater agreement between VN-NP and vascular neurologist assessments were excellent, ranging from 0.9 to 1.0. The duration of VN-NP consultation was 53.2 +/- 9.0 minutes, which included the vascular neurologist supervisory evaluation time of 12.0 +/- 9.6 minutes. Conclusion. This study illustrated that a stroke center VN-NP, in partnership with a vascular neurologist, could deliver timely telemedicine consultations, accurate diagnoses, and correct treatments in acute stroke patients who presented to remotely located rural emergency departments within a hub and spoke network. VN-NPs may fulfill the role of a telestroke provider.

Applying of the Artificial Neural Networks (ANN) to Identify and Characterize Sweet Spots in Shale Gas Formations

Science.gov (United States)

Puskarczyk, Edyta

2018-03-01

The main goal of the study was to enhance and improve information about the Ordovician and Silurian gas-saturated shale formations. Author focused on: firstly, identification of the shale gas formations, especially the sweet spots horizons, secondly, classification and thirdly, the accurate characterization of divisional intervals. Data set comprised of standard well logs from the selected well. Shale formations are represented mainly by claystones, siltstones, and mudstones. The formations are also partially rich in organic matter. During the calculations, information about lithology of stratigraphy weren't taken into account. In the analysis, selforganizing neural network - Kohonen Algorithm (ANN) was used for sweet spots identification. Different networks and different software were tested and the best network was used for application and interpretation. As a results of Kohonen networks, groups corresponding to the gas-bearing intervals were found. The analysis showed diversification between gas-bearing formations and surrounding beds. It is also shown that internal diversification in sweet spots is present. Kohonen algorithm was also used for geological interpretation of well log data and electrofacies prediction. Reliable characteristic into groups shows that Ja Mb and Sa Fm which are usually treated as potential sweet spots only partially have good reservoir conditions. It is concluded that ANN appears to be useful and quick tool for preliminary classification of members and sweet spots identification.

Overexpression of Mitofusin 2 inhibited oxidized low-density lipoprotein induced vascular smooth muscle cell proliferation and reduced atherosclerotic lesion formation in rabbit

International Nuclear Information System (INIS)

Guo Yanhong; Chen Kuanghueih; Gao Wei; Li Qian; Chen Li; Wang Guisong; Tang Jian

2007-01-01

Our previous studies have implies that Mitofusin 2 (Mfn2), which was progressively reduced in arteries from ApoE -/- mice during the development of atherosclerosis, may take part in pathogenesis of atherosclerosis. In this study, we found that overexpression of Mfn2 inhibited oxidized low-density lipoprotein or serum induced vascular smooth muscle cell proliferation by down-regulation of Akt and ERK phosphorylation. Then we investigated the in vivo role of Mfn2 on the development of atherosclerosis in rabbits using adenovirus expressing Mitofusin 2 gene (AdMfn2). By morphometric analysis we found overexpression of Mfn2 inhibited atherosclerotic lesion formation and intima/media ratio by 66.7% and 74.6%, respectively, compared with control group. These results suggest that local Mfn2 treatment suppresses the development of atherosclerosis in vivo in part by attenuating the smooth muscle cell proliferation induced by lipid deposition and vascular injury

Cytoskeletal actin dynamics shape a ramifying actin network underpinning immunological synapse formation

DEFF Research Database (Denmark)

Fritzsche, Marco; Fernandes, Ricardo A.; Chang, Veronica T.

2017-01-01

optical microscopes to analyze resting and activated T cells, we show that, following contact formation with activating surfaces, these cells sequentially rearrange their cortical actin across the entire cell, creating a previously unreported ramifying actin network above the immunological synapse...

CAPILLARY NETWORK ANOMALIES IN BRANCH RETINAL VEIN OCCLUSION ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

Science.gov (United States)

Rispoli, Marco; Savastano, Maria Cristina; Lumbroso, Bruno

2015-11-01

To analyze the foveal microvasculature features in eyes with branch retinal vein occlusion (BRVO) using optical coherence tomography angiography based on split spectrum amplitude decorrelation angiography technology. A total of 10 BRVO eyes (mean age 64.2 ± 8.02 range between 52 years and 76 years) were evaluated by optical coherence tomography angiography (XR-Avanti; Optovue). The macular angiography scan protocol covered a 3 mm × 3 mm area. The focus of angiography analysis were two retinal layers: superficial vascular network and deep vascular network. The following vascular morphological congestion parameters were assessed in the vein occlusion area in both the superficial and deep networks: foveal avascular zone enlargement, capillary non-perfusion occurrence, microvascular abnormalities appearance, and vascular congestion signs. Image analyses were performed by 2 masked observers and interobserver agreement of image analyses was 0.90 (κ = 0.225, P network of BRVO, a decrease in capillary density with foveal avascular zone enlargement, capillary non-perfusion occurrence, and microvascular abnormalities appearance was observed (P network showed the main vascular congestion at the boundary between healthy and nonperfused retina. Optical coherence tomography angiography in BRVO allows to detect foveal avascular zone enlargement, capillary nonperfusion, microvascular abnormalities, and vascular congestion signs both in the superficial and deep capillary network in all eyes. Optical coherence tomography angiography technology is a potential clinical tool for BRVO diagnosis and follow-up, providing stratigraphic vascular details that have not been previously observed by standard fluorescein angiography. The normal retinal vascular nets and areas of nonperfusion and congestion can be identified at various retinal levels. Optical coherence tomography angiography provides noninvasive images of the retinal capillaries and vascular networks.

Formation of nanoscale networks: selectively swelling amphiphilic block copolymers with CO2-expanded liquids.

Science.gov (United States)

Gong, Jianliang; Zhang, Aijuan; Bai, Hua; Zhang, Qingkun; Du, Can; Li, Lei; Hong, Yanzhen; Li, Jun

2013-02-07

Polymeric films with nanoscale networks were prepared by selectively swelling an amphiphilic diblock copolymer, polystyrene-block-poly(4-vinylpyridine) (PS-b-P4VP), with the CO(2)-expanded liquid (CXL), CO(2)-methanol. The phase behavior of the CO(2)-methanol system was investigated by both theoretical calculation and experiments, revealing that methanol can be expanded by CO(2), forming homogeneous CXL under the experimental conditions. When treated with the CO(2)-methanol system, the spin cast compact PS-b-P4VP film was transformed into a network with interconnected pores, in a pressure range of 12-20 MPa and a temperature range of 45-60 °C. The formation mechanism of the network, involving plasticization of PS and selective swelling of P4VP, was proposed. Because the diblock copolymer diffusion process is controlled by the activated hopping of individual block copolymer chains with the thermodynamic barrier for moving PVP segments from one to another, the formation of the network structures is achieved in a short time scale and shows "thermodynamically restricted" character. Furthermore, the resulting polymer networks were employed as templates, for the preparation of polypyrrole networks, by an electrochemical polymerization process. The prepared porous polypyrrole film was used to fabricate a chemoresistor-type gas sensor which showed high sensitivity towards ammonia.

Effect of hydro mechanical coupling on natural fracture network formation in sedimentary basins

Science.gov (United States)

Ouraga, Zady; Guy, Nicolas; Pouya, Amade

2018-05-01

In sedimentary basin context, numerous phenomena, depending on the geological time span, can result in natural fracture network formation. In this paper, fracture network and dynamic fracture spacing triggered by significant sedimentation rate are studied considering mode I fracture propagation using a coupled hydro-mechanical numerical methods. The focus is put on synthetic geological structure under a constant sedimentation rate on its top. This model contains vertical fracture network initially closed and homogeneously distributed. The fractures are modelled with cohesive zone model undergoing damage and the flow is described by Poiseuille's law. The effect of the behaviour of the rock is studied and the analysis leads to a pattern of fracture network and fracture spacing in the geological layer.

The vascular basement membrane as "soil" in brain metastasis.

Directory of Open Access Journals (Sweden)

W Shawn Carbonell

2009-06-01

Full Text Available Brain-specific homing and direct interactions with the neural substance are prominent hypotheses for brain metastasis formation and a modern manifestation of Paget's "seed and soil" concept. However, there is little direct evidence for this "neurotropic" growth in vivo. In contrast, many experimental studies have anecdotally noted the propensity of metastatic cells to grow along the exterior of pre-existing vessels of the CNS, a process termed vascular cooption. These observations suggest the "soil" for malignant cells in the CNS may well be vascular, rather than neuronal. We used in vivo experimental models of brain metastasis and analysis of human clinical specimens to test this hypothesis. Indeed, over 95% of early micrometastases examined demonstrated vascular cooption with little evidence for isolated neurotropic growth. This vessel interaction was adhesive in nature implicating the vascular basement membrane (VBM as the active substrate for tumor cell growth in the brain. Accordingly, VBM promoted adhesion and invasion of malignant cells and was sufficient for tumor growth prior to any evidence of angiogenesis. Blockade or loss of the beta1 integrin subunit in tumor cells prevented adhesion to VBM and attenuated metastasis establishment and growth in vivo. Our data establishes a new understanding of CNS metastasis formation and identifies the neurovasculature as the critical partner for such growth. Further, we have elucidated the mechanism of vascular cooption for the first time. These findings may help inform the design of effective molecular therapies for patients with fatal CNS malignancies.

Understanding the process of social network evolution: Online-offline integrated analysis of social tie formation.

Science.gov (United States)

Kwak, Doyeon; Kim, Wonjoon

2017-01-01

It is important to consider the interweaving nature of online and offline social networks when we examine social network evolution. However, it is difficult to find any research that examines the process of social tie formation from an integrated perspective. In our study, we quantitatively measure offline interactions and examine the corresponding evolution of online social network in order to understand the significance of interrelationship between online and offline social factors in generating social ties. We analyze the radio signal strength indicator sensor data from a series of social events to understand offline interactions among the participants and measure the structural attributes of their existing online Facebook social networks. By monitoring the changes in their online social networks before and after offline interactions in a series of social events, we verify that the ability to develop an offline interaction into an online friendship is tied to the number of social connections that participants previously had, while the presence of shared mutual friends between a pair of participants disrupts potential new connections within the pre-designed offline social events. Thus, while our integrative approach enables us to confirm the theory of preferential attachment in the process of network formation, the common neighbor theory is not supported. Our dual-dimensional network analysis allows us to observe the actual process of social network evolution rather than to make predictions based on the assumption of self-organizing networks.

Understanding the process of social network evolution: Online-offline integrated analysis of social tie formation.

Directory of Open Access Journals (Sweden)

Doyeon Kwak

Full Text Available It is important to consider the interweaving nature of online and offline social networks when we examine social network evolution. However, it is difficult to find any research that examines the process of social tie formation from an integrated perspective. In our study, we quantitatively measure offline interactions and examine the corresponding evolution of online social network in order to understand the significance of interrelationship between online and offline social factors in generating social ties. We analyze the radio signal strength indicator sensor data from a series of social events to understand offline interactions among the participants and measure the structural attributes of their existing online Facebook social networks. By monitoring the changes in their online social networks before and after offline interactions in a series of social events, we verify that the ability to develop an offline interaction into an online friendship is tied to the number of social connections that participants previously had, while the presence of shared mutual friends between a pair of participants disrupts potential new connections within the pre-designed offline social events. Thus, while our integrative approach enables us to confirm the theory of preferential attachment in the process of network formation, the common neighbor theory is not supported. Our dual-dimensional network analysis allows us to observe the actual process of social network evolution rather than to make predictions based on the assumption of self-organizing networks.

Angiogenesis and anti-angiogenesis: Perspectives for the treatment of solid tumors

NARCIS (Netherlands)

Hinsbergh, V.W.M. van; Collen, A.; Koolwijk, P.

1999-01-01

Angiogenesis is the formation of new blood vessels from preexisting ones. Many solid tumors depend on an extensive newly formed vascular network to become nourished and to expand. Tumor cells induce the formation of an extensive but aberrant vascular network by the secretion of angiogenic factors. A

Digital-Networked Images as Personal Acts of Political Expression: New Categories for Meaning Formation

Directory of Open Access Journals (Sweden)

Mona Kasra

2017-12-01

Full Text Available This article examines the growing use of digital-networked images, specifically online self-portraits or “selfies”, as deliberate and personal acts of political expression and the ways in which meaning evolves and expands from their presence on the Internet. To understand the role of digital-networked images as a site for engaging in a personal and connective “visual” action that leads to formation of transient communities, the author analyzes the nude self-portrait of the young Egyptian woman Aliaa Magda Elmahdy, which during the Egyptian uprisings in 2011 drew attention across social media. As an object of analysis this image is a prime example of the use of digital-networked images in temporally intentional distribution, and as an instance of political enactment unique to this era. This article also explains the concept of participatory narratives as an ongoing process of meaning formation in the digital-networked image, shaped by the fluidity of the multiple and immediate textual narratives, visual derivatives, re-appropriation, and remixes contributed by other interested viewers. The online circulation of digital-networked images in fact culminates in a flow of ever-changing and overarching narratives, broadening the contextual scope around which images are traditionally viewed.

It’s all about networking! Empirical investigation of social capital formation on social network sites

OpenAIRE

Koroleva, Ksenia; Krasnova, Hanna; Veltri, Natasha F.; Günther, Oliver

2011-01-01

As Social Network Sites (SNS) permeate our daily routines, the question whether participation results in value for SNS users becomes particularly acute. This study adopts a 'participation-source-outcome' perspective to explore how distinct uses of SNS generate various types of social capital benefits. Building on existing research, extensive qualitative findings and an empirical study with 253 Facebook users, we uncover the process of social capital formation on SNS. We find that even though ...

Fractal Branching in Vascular Trees and Networks by VESsel GENeration Analysis (VESGEN)

Science.gov (United States)

Parsons-Wingerter, Patricia A.

2016-01-01

Vascular patterning offers an informative multi-scale, fractal readout of regulatory signaling by complex molecular pathways. Understanding such molecular crosstalk is important for physiological, pathological and therapeutic research in Space Biology and Astronaut countermeasures. When mapped out and quantified by NASA's innovative VESsel GENeration Analysis (VESGEN) software, remodeling vascular patterns become useful biomarkers that advance out understanding of the response of biology and human health to challenges such as microgravity and radiation in space environments.

The impact of various scaffold components on vascularized bone constructs.

Science.gov (United States)

Eweida, Ahmad; Schulte, Matthias; Frisch, Oliver; Kneser, Ulrich; Harhaus, Leila

2017-06-01

Bone tissue engineering is gaining more interest in the field of craniofacial surgery where continuous efforts are being made to improve the outcomes via modulation of the scaffold components. In an in vitro three dimensional (3D) culture, the effect of bone morphogenic protein 2 (BMP2, 60 μg/ml) and the effect of different cell seeding densities (0.25, 0.5, and 1 × 104) of rat mesenchymal stem cells seeded on nanocrystalline hydroxyapatite in silica gel matrix (Nanobone ® ) on the cell viability and differentiation were studied. Alkaline phosphatase and viability assays were performed at day 7, day 14, and day 21 to assess the differentiation and the relative fraction of viable cells in the 3D cell cultures. In a subsequent in vivo study, we examined the effect of axial vascularization, the scaffold's particle size and the nature of the matrix (collagen type I vs. diluted fibrin) on vascularization and tissue generation in vascularized bone construct in rats. Regarding vascularization, we compared constructs vascularized randomly by extrinsic vascularization from the periphery of the implanted construct with others vascularized axially via an implanted arteriovenous loop (AVL). Regarding the particle size, we compared constructs having a scaffold particle size of 0.2 mm (powder) with other constructs having a particle size of 2 × 0.6 mm (granules). Regarding the matrix we compared constructs having a collagen matrix with others having a fibrin matrix. Various groups were compared regarding the amount of tissue generation, vascularization, and cellular proliferation. The initial seeding density had a temporary and minimal effect on the overall osteogenic differentiation of the cells. On the contrary, adding BMP2 in a concentration of 60 μg/ml over one week led to an overall enhanced osteogenic differentiation despite depressed cell viability. Axial vascularization was mandatory for efficient tissue formation and vascularization of the bone construct

Ising-based model of opinion formation in a complex network of interpersonal interactions

Science.gov (United States)

Grabowski, A.; Kosiński, R. A.

2006-03-01

In our work the process of opinion formation in the human population, treated as a scale-free network, is modeled and investigated numerically. The individuals (nodes of the network) are characterized by their authorities, which influence the interpersonal interactions in the population. Hierarchical, two-level structures of interpersonal interactions and spatial localization of individuals are taken into account. The effect of the mass media, modeled as an external stimulation acting on the social network, on the process of opinion formation is investigated. It was found that in the time evolution of opinions of individuals critical phenomena occur. The first one is observed in the critical temperature of the system TC and is connected with the situation in the community, which may be described by such quantifiers as the economic status of people, unemployment or crime wave. Another critical phenomenon is connected with the influence of mass media on the population. As results from our computations, under certain circumstances the mass media can provoke critical rebuilding of opinions in the population.

Mapping and Quantification of Vascular Branching in Plants, Animals and Humans by VESGEN Software

Science.gov (United States)

Parsons-Wingerter, P. A.; Vickerman, M. B.; Keith, P. A.

2010-01-01

Humans face daunting challenges in the successful exploration and colonization of space, including adverse alterations in gravity and radiation. The Earth-determined biology of plants, animals and humans is significantly modified in such extraterrestrial environments. One physiological requirement shared by larger plants and animals with humans is a complex, highly branching vascular system that is dynamically responsive to cellular metabolism, immunological protection and specialized cellular/tissue function. VESsel GENeration (VESGEN) Analysis has been developed as a mature beta version, pre-release research software for mapping and quantification of the fractal-based complexity of vascular branching. Alterations in vascular branching pattern can provide informative read-outs of altered vascular regulation. Originally developed for biomedical applications in angiogenesis, VESGEN 2D has provided novel insights into the cytokine, transgenic and therapeutic regulation of angiogenesis, lymphangiogenesis and other microvascular remodeling phenomena. Vascular trees, networks and tree-network composites are mapped and quantified. Applications include disease progression from clinical ophthalmic images of the human retina; experimental regulation of vascular remodeling in the mouse retina; avian and mouse coronary vasculature, and other experimental models in vivo. We envision that altered branching in the leaves of plants studied on ISS such as Arabidopsis thaliana cans also be analyzed.

Biophysical induction of vascular smooth muscle cell podosomes.

Directory of Open Access Journals (Sweden)

Na Young Kim

Full Text Available Vascular smooth muscle cell (VSMC migration and matrix degradation occurs with intimal hyperplasia associated with atherosclerosis, vascular injury, and restenosis. One proposed mechanism by which VSMCs degrade matrix is through the use of podosomes, transient actin-based structures that are thought to play a role in extracellular matrix degradation by creating localized sites of matrix metalloproteinase (MMP secretion. To date, podosomes in VSMCs have largely been studied by stimulating cells with phorbol esters, such as phorbol 12,13-dibutyrate (PDBu, however little is known about the physiological cues that drive podosome formation. We present the first evidence that physiological, physical stimuli mimicking cues present within the microenvironment of diseased arteries can induce podosome formation in VSMCs. Both microtopographical cues and imposed pressure mimicking stage II hypertension induce podosome formation in A7R5 rat aortic smooth muscle cells. Moreover, wounding using a scratch assay induces podosomes at the leading edge of VSMCs. Notably the effect of each of these biophysical stimuli on podosome stimulation can be inhibited using a Src inhibitor. Together, these data indicate that physical cues can induce podosome formation in VSMCs.

Cohesive subgroup formation : enabling and constraining effects of social capital in strategic technology alliance networks

NARCIS (Netherlands)

Duysters, G.M.; Lemmens, C.E.A.V.

2002-01-01

In this paper we will examine the role of embeddedness and social capital in the process of cohesive subgroup formation in strategic technology alliance networks. More in particular, we will investigate the social mechanisms that enable and enforce cohesive subgroup formation. We will argue that the

Glass formation via structural fragmentation of a 2D coordination network.

Science.gov (United States)

Umeyama, D; Funnell, N P; Cliffe, M J; Hill, J A; Goodwin, A L; Hijikata, Y; Itakura, T; Okubo, T; Horike, S; Kitagawa, S

2015-08-18

The structure of a glass obtained by the melt quenching of a two-dimensional (2D) coordination network was examined. X-ray analyses disclosed a 2D-to-0D structural transformation before and after glass formation. The mechanism is unique to coordination compounds, as it is characterized by labile and flexible coordination bonds.

Enhancing Tumor Drug Delivery by Laser-Activated Vascular Barrier Disruption

Science.gov (United States)

2009-12-01

diabetic retinopathy . Therefore, se- lectively targeting existing blood vessels (vascular- disrupting therapy) and/or inhibiting the forma- tion of new...adhesion led to the formation of thrombi that can occlude blood vessels, causing vascular shutdown. However, viable tumor cells were often detected at...tumor sections (Fig. 4). However, viable tumor cells were commonly detected at tumor periphery. Because of the existence of viable peripheral tumor cells

Bmp2 in osteoblasts of periosteum and trabecular bone links bone formation to vascularization and mesenchymal stem cells

Science.gov (United States)

Yang, Wuchen; Guo, Dayong; Harris, Marie A.; Cui, Yong; Gluhak-Heinrich, Jelica; Wu, Junjie; Chen, Xiao-Dong; Skinner, Charles; Nyman, Jeffry S.; Edwards, James R.; Mundy, Gregory R.; Lichtler, Alex; Kream, Barbara E.; Rowe, David W.; Kalajzic, Ivo; David, Val; Quarles, Darryl L.; Villareal, Demetri; Scott, Greg; Ray, Manas; Liu, S.; Martin, James F.; Mishina, Yuji; Harris, Stephen E.

2013-01-01

Summary We generated a new Bmp2 conditional-knockout allele without a neo cassette that removes the Bmp2 gene from osteoblasts (Bmp2-cKOob) using the 3.6Col1a1-Cre transgenic model. Bones of Bmp2-cKOob mice are thinner, with increased brittleness. Osteoblast activity is reduced as reflected in a reduced bone formation rate and failure to differentiate to a mature mineralizing stage. Bmp2 in osteoblasts also indirectly controls angiogenesis in the periosteum and bone marrow. VegfA production is reduced in Bmp2-cKOob osteoblasts. Deletion of Bmp2 in osteoblasts also leads to defective mesenchymal stem cells (MSCs), which correlates with the reduced microvascular bed in the periosteum and trabecular bones. Expression of several MSC marker genes (α-SMA, CD146 and Angiopoietin-1) in vivo, in vitro CFU assays and deletion of Bmp2 in vitro in α-SMA+ MSCs support our conclusions. Critical roles of Bmp2 in osteoblasts and MSCs are a vital link between bone formation, vascularization and mesenchymal stem cells. PMID:23843612

Project team formation support for self-directed learners in social learning networks

NARCIS (Netherlands)

Spoelstra, Howard; Van Rosmalen, Peter; Sloep, Peter

2012-01-01

Spoelstra, H., Van Rosmalen, P., & Sloep, P. B. (2012). Project team formation support for self-directed learners in social learning networks. In P. Kommers, P. Isaias, & N. Bessis (Eds.), Proceedings of the IADIS International Conference on Web Based Communities and Social Media (ICWBC & SM 2012)

Formation of Molecular Networks: Tailored Quantum Boxes and Behavior of Adsorbed CO in Them

Science.gov (United States)

Wyrick, Jon; Sun, Dezheng; Kim, Dae-Ho; Cheng, Zhihai; Lu, Wenhao; Zhu, Yeming; Luo, Miaomiao; Kim, Yong Su; Rotenberg, Eli; Kim, Kwangmoo; Einstein, T. L.; Bartels, Ludwig

2011-03-01

We show that the behavior of CO adsorbed into the pores of large regular networks on Cu(111) is significantly affected by their nano-scale lateral confinement and that formation of the networks themselves is directed by the Shockley surface state. Saturation coverages of CO are found to exhibit persistent dislocation lines; at lower coverages their mobility increases. Individual CO within the pores titrate the surface state, providing crucial information for understanding formation of the network as a result of optimization of the number N of electrons bound within each pore. Determination of N is based on quinone-coverage-dependent UPS data and an analysis of states of particles in a pore-shaped box (verified by CO's titration); a wide range of possible pore shapes and sizes has been considered. Work at UCR supported by NSF CHE 07-49949; at UMD by NSF CHE 07-50334 & UMD NSF-MRSEC DMR 05-20471.

Vascular Neurology Nurse Practitioner Provision of Telemedicine Consultations

Directory of Open Access Journals (Sweden)

Bart M. Demaerschalk

2010-01-01

Full Text Available Objective. The objective was to define and evaluate a role for the Vascular Neurology-Nurse Practitioner (VN-NP in the delivery of telemedicine consultations in partnership with a vascular neurologist. Methods. Prospective stroke alert patients at participating hospitals underwent a two-way audio video telemedicine consultation with a VN-NP at a remotely located stroke center in partnership with a vascular neurologist. Demographic information, National Institutes of Health Stroke Scale (NIHSS scores, diagnoses, CT contraindications to thrombolysis, thrombolysis eligibility, and time interval data were collected. The inter-rater agreement between VN-NP and vascular neurologist assessments was calculated. Results. Ten patients were evaluated. Four were determined to have ischemic stroke, one had a transient ischemic attack, two had intracerebral hemorrhages, and three were stroke mimics. Overall, three patients received thrombolysis. The inter-rater agreement between VN-NP and vascular neurologist assessments were excellent, ranging from 0.9 to 1.0. The duration of VN-NP consultation was 53.2±9.0 minutes, which included the vascular neurologist supervisory evaluation time of 12.0±9.6 minutes. Conclusion. This study illustrated that a stroke center VN-NP, in partnership with a vascular neurologist, could deliver timely telemedicine consultations, accurate diagnoses, and correct treatments in acute stroke patients who presented to remotely located rural emergency departments within a hub and spoke network. VN-NPs may fulfill the role of a telestroke provider.

Wireless network interface energy consumption implications of popular streaming formats

Science.gov (United States)

Chandra, Surendar

2001-12-01

With the proliferation of mobile streaming multimedia, available battery capacity constrains the end-user experience. Since streaming applications tend to be long running, wireless network interface card's (WNIC) energy consumption is particularly an acute problem. In this work, we explore the WNIC energy consumption implications of popular multimedia streaming formats from Microsoft (Windows media), Real (Real media) and Apple (Quick Time). We investigate the energy consumption under varying stream bandwidth and network loss rates. We also explore history-based client-side strategies to reduce the energy consumed by transitioning the WNICs to a lower power consuming sleep state. We show that Microsoft media tends to transmit packets at regular intervals; streams optimized for 28.8 Kbps can save over 80% in energy consumption with 2% data loss. A high bandwidth stream (768 Kbps) can still save 57% in energy consumption with less than 0.3% data loss. For high bandwidth streams, Microsoft media exploits network-level packet fragmentation, which can lead to excessive packet loss (and wasted energy) in a lossy network. Real stream packets tend to be sent closer to each other, especially at higher bandwidths. Quicktime packets sometimes arrive in quick succession; most likely an application level fragmentation mechanism. Such packets are harder to predict at the network level without understanding the packet semantics.

Simultaneous wavelength and format conversion in SDN/NFV for flexible optical network based on FWM in SOA

Science.gov (United States)

Zhan, Yueying; Wang, Danshi; Zhang, Min

2018-04-01

We propose an all-optical wavelength and format conversion model (CM) for a dynamic data center interconnect node and coherent passive optical network (PON) optical network unit (ONU) in software-defined networking and network function virtualization system based on four-wave mixing in a semiconductor optical amplifier. Five wavelength converted DQPSK signals and two format converted DPSK signals are generated; the performances of the generated signals for two strategies of setting CM in the data center interconnect node and coherent PON ONU, which are over 10 km fiber transmission, have been verified. All of the converted signals are with a power penalty less than 2.2 dB at FEC threshold of 3.8 × 10 - 3, and the optimum bias current of SOA is 300 mA.

3,3'Diindolylmethane suppresses vascular smooth muscle cell phenotypic modulation and inhibits neointima formation after carotid injury.

Directory of Open Access Journals (Sweden)

Hongjing Guan

Full Text Available 3,3'Diindolylmethane (DIM, a natural phytochemical, has shown inhibitory effects on the growth and migration of a variety of cancer cells; however, whether DIM has similar effects on vascular smooth muscle cells (VSMCs remains unknown. The purpose of this study was to assess the effects of DIM on the proliferation and migration of cultured VSMCs and neointima formation in a carotid injury model, as well as the related cell signaling mechanisms.DIM dose-dependently inhibited the platelet-derived growth factor (PDGF-BB-induced proliferation of VSMCs without cell cytotoxicity. This inhibition was caused by a G0/G1 phase cell cycle arrest demonstrated by fluorescence-activated cell-sorting analysis. We also showed that DIM-induced growth inhibition was associated with the inhibition of the expression of cyclin D1 and cyclin-dependent kinase (CDK 4/6 as well as an increase in p27(Kip1 levels in PDGF-stimulated VSMCs. Moreover, DIM was also found to modulate migration of VSMCs and smooth muscle-specific contractile marker expression. Mechanistically, DIM negatively modulated PDGF-BB-induced phosphorylation of PDGF-recptorβ (PDGF-Rβ and the activities of downstream signaling molecules including Akt/glycogen synthase kinase(GSK3β, extracellular signal-regulated kinase1/2 (ERK1/2, and signal transducers and activators of transcription 3 (STAT3. Our in vivo studies using a mouse carotid arterial injury model revealed that treatment with 150 mg/kg DIM resulted in significant reduction of the neointima/media ratio and proliferating cell nuclear antigen (PCNA-positive cells, without affecting apoptosis of vascular cells and reendothelialization. Infiltration of inflammatory cells was also inhibited by DIM administration.These results demonstrate that DIM can suppress the phenotypic modulation of VSMCs and neointima hyperplasia after vascular injury. These beneficial effects on VSMCs were at least partly mediated by the inhibition of PDGF-Rβ and the

Low Immunogenic Endothelial Cells Maintain Morphological and Functional Properties Required for Vascular Tissue Engineering.

Science.gov (United States)

Lau, Skadi; Eicke, Dorothee; Carvalho Oliveira, Marco; Wiegmann, Bettina; Schrimpf, Claudia; Haverich, Axel; Blasczyk, Rainer; Wilhelmi, Mathias; Figueiredo, Constança; Böer, Ulrike

2018-03-01

The limited availability of native vessels suitable for the application as hemodialysis shunts or bypass material demands new strategies in cardiovascular surgery. Tissue-engineered vascular grafts containing autologous cells are considered ideal vessel replacements due to the low risk of rejection. However, endothelial cells (EC), which are central components of natural blood vessels, are difficult to obtain from elderly patients of poor health. Umbilical cord blood represents a promising alternative source for EC, but their allogeneic origin corresponds with the risk of rejection after allotransplantation. To reduce this risk, the human leukocyte antigen class I (HLA I) complex was stably silenced by lentiviral vector-mediated RNA interference (RNAi) in EC from peripheral blood and umbilical cord blood and vein. EC from all three sources were transduced by 93.1% ± 4.8% and effectively, HLA I-silenced by up to 67% compared to nontransduced (NT) cells or transduced with a nonspecific short hairpin RNA, respectively. Silenced EC remained capable to express characteristic endothelial surface markers such as CD31 and vascular endothelial cadherin important for constructing a tight barrier, as well as von Willebrand factor and endothelial nitric oxide synthase important for blood coagulation and vessel tone regulation. Moreover, HLA I-silenced EC were still able to align under unidirectional flow, to take up acetylated low-density lipoprotein, and to form capillary-like tube structures in three-dimensional fibrin gels similar to NT cells. In particular, addition of adipose tissue-derived mesenchymal stem cells significantly improved tube formation capability of HLA I-silenced EC toward long and widely branched vascular networks necessary for prevascularizing vascular grafts. Thus, silencing HLA I by RNAi represents a promising technique to reduce the immunogenic potential of EC from three different sources without interfering with EC-specific morphological and

Deficiency of the NR4A Orphan Nuclear Receptor NOR1 attenuates Neointima Formation Following Vascular Injury

Science.gov (United States)

Nomiyama, Takashi; Zhao, Yue; Gizard, Florence; Findeisen, Hannes M.; Heywood, Elizabeth B.; Jones, Karrie L.; Conneely, Orla M.; Bruemmer, Dennis

2009-01-01

Background The neuron-derived orphan receptor-1 (NOR1) belongs to the evolutionary highly conserved and most ancient NR4A subfamily of the nuclear hormone receptor superfamily. Members of this subfamily function as early response genes regulating key cellular processes including proliferation, differentiation, and survival. Although NOR1 has previously been demonstrated to be required for smooth muscle cell (SMC) proliferation in vitro, the role of this nuclear receptor for the proliferative response underlying neointima formation and target genes trans-activated by NOR1 remain to be defined. Methods and Results Using a model of guide wire-induced arterial injury, we demonstrate decreased neointima formation in NOR1-/- mice compared to wildtype mice. In vitro, NOR1-deficient SMC exhibit decreased proliferation due to a G1→S phase arrest of the cell cycle and increased apoptosis in response to serum deprivation. NOR1-deficiency alters phosphorylation of the retinoblastoma protein by preventing mitogen-induced cyclin D1 and D2 expression. Conversely, overexpression of NOR1 induces cyclin D1 expression and the transcriptional activity of the cyclin D1 promoter in transient reporter assays. Gel shift and chromatin immunoprecipitation assays identified a putative response element for NR4A receptors in the cyclin D1 promoter, to which NOR1 is recruited in response to mitogenic stimulation. Finally, we provide evidence that these observations are applicable in vivo by demonstrating decreased cyclin D1 expression during neointima formation in NOR1-deficient mice. Conclusions These experiments characterize cyclin D1 as a NOR1-regulated target gene in SMC and demonstrate that NOR1 deficiency decreases neointima formation in response to vascular injury. PMID:19153266

Transforming growth factor β family members in regulation of vascular function: in the light of vascular conditional knockouts.

Science.gov (United States)

Jakobsson, Lars; van Meeteren, Laurens A

2013-05-15

Blood vessels are composed of endothelial cells, mural cells (smooth muscle cells and pericytes) and their shared basement membrane. During embryonic development a multitude of signaling components orchestrate the formation of new vessels. The process is highly dependent on correct dosage, spacing and timing of these signaling molecules. As vessels mature some cascades remain active, albeit at very low levels, and may be reactivated upon demand. Members of the Transforming growth factor β (TGF-β) protein family are strongly engaged in developmental angiogenesis but are also regulators of vascular integrity in the adult. In humans various genetic alterations within this protein family cause vascular disorders, involving disintegration of vascular integrity. Here we summarize and discuss recent data gathered from conditional and endothelial cell specific genetic loss-of-function of members of the TGF-β family in the mouse. Copyright © 2013 Elsevier Inc. All rights reserved.

The formation of synchronization cliques during the development of modular neural networks

International Nuclear Information System (INIS)

Fuchs, Einat; Ayali, Amir; Ben-Jacob, Eshel; Boccaletti, Stefano

2009-01-01

Modular organization is a special feature shared by many biological and social networks alike. It is a hallmark for systems exhibiting multitasking, in which individual tasks are performed by separated and yet coordinated functional groups. Understanding how networks of segregated modules develop to support coordinated multitasking functionalities is the main topic of the current study. Using simulations of biologically inspired neuronal networks during development, we study the formation of functional groups (cliques) and inter-neuronal synchronization. The results indicate that synchronization cliques first develop locally according to the explicit network topological organization. Later on, at intermediate connectivity levels, when networks have both local segregation and long-range integration, new synchronization cliques with distinctive properties are formed. In particular, by defining a new measure of synchronization centrality, we identify at these developmental stages dominant neurons whose functional centrality largely exceeds the topological one. These are generated mainly in a few dominant clusters that become the centers of the newly formed synchronization cliques. We show that by the local synchronization properties at the very early developmental stages, it is possible to predict with high accuracy which clusters will become dominant in later stages of network development

Longitudinal visualization of vascular occlusion, reperfusion, and remodeling in a zebrafish model of retinal vascular leakage using OCT angiography

Science.gov (United States)

Spitz, Kathleen; Bozic, Ivan; Desai, Vineet; Rao, Gopikrishna M.; Pollock, Lana M.; Anand-Apte, Bela; Tao, Yuankai K.

2017-02-01

Diabetic retinopathy (DR) and age-related macular degeneration (AMD) are two of the leading causes of blindness and visual impairment in the world. Neovascularization results in severe vision loss in DR and AMD and, thus, there is an unmet need to identify mechanisms of pathogenesis and novel anti-angiogenic therapies. Zebrafish is a leading model organism for studying human disease pathogenesis, and the highly conserved drug activity between zebrafish and humans and their ability to readily absorb small molecules dissolved in water has benefited pharmaceutical discovery. Here, we use optical coherence tomography (OCT) and OCT angiography (OCT-A) to perform noninvasive, in vivo retinal imaging in a zebrafish model of vascular leakage. Zebrafish were treated with diethylaminobenzaldehyde (DEAB) to induce vascular leakage and imaged with OCT and OCT-A at six time points over two weeks: baseline one day before treatment and one, three, six, eight, and ten days post treatment. Longitudinal functional imaging showed significant vascular response immediately after DEAB treatment. Observed vascular changes included partial or complete vascular occlusion immediately after treatment and reperfusion during a two-week period. Increased vascular tortuosity several days post treatment indicated remodeling, and bifurcations and collateral vessel formation were also observed. In addition, significant treatment response variabilities were observed in the contralateral eye of the same animal. Anatomical and functional normalization was observed in most animals by ten days post treatment. These preliminary results motivate potential applications of OCT-A as a tool for studying pathogenesis and therapeutic screening in zebrafish models of retinal vascular disease.

Notes on a PDE system for biological network formation

KAUST Repository

Haskovec, Jan

2016-01-22

We present new analytical and numerical results for the elliptic–parabolic system of partial differential equations proposed by Hu and Cai, which models the formation of biological transport networks. The model describes the pressure field using a Darcy’s type equation and the dynamics of the conductance network under pressure force effects. Randomness in the material structure is represented by a linear diffusion term and conductance relaxation by an algebraic decay term. The analytical part extends the results of Haskovec et al. (2015) regarding the existence of weak and mild solutions to the whole range of meaningful relaxation exponents. Moreover, we prove finite time extinction or break-down of solutions in the spatially one-dimensional setting for certain ranges of the relaxation exponent. We also construct stationary solutions for the case of vanishing diffusion and critical value of the relaxation exponent, using a variational formulation and a penalty method. The analytical part is complemented by extensive numerical simulations. We propose a discretization based on mixed finite elements and study the qualitative properties of network structures for various parameter values. Furthermore, we indicate numerically that some analytical results proved for the spatially one-dimensional setting are likely to be valid also in several space dimensions.

In-silico analysis on biofabricating vascular networks using kinetic Monte Carlo simulations

International Nuclear Information System (INIS)

Sun, Yi; Yang, Xiaofeng; Wang, Qi

2014-01-01

We present a computational modeling approach to study the fusion of multicellular aggregate systems in a novel scaffold-less biofabrication process, known as ‘bioprinting’. In this novel technology, live multicellular aggregates are used as fundamental building blocks to make tissues or organs (collectively known as the bio-constructs,) via the layer-by-layer deposition technique or other methods; the printed bio-constructs embedded in maturogens, consisting of nutrient-rich bio-compatible hydrogels, are then placed in bioreactors to undergo the cellular aggregate fusion process to form the desired functional bio-structures. Our approach reported here is an agent-based modeling method, which uses the kinetic Monte Carlo (KMC) algorithm to evolve the cellular system on a lattice. In this method, the cells and the hydrogel media, in which cells are embedded, are coarse-grained to material’s points on a three-dimensional (3D) lattice, where the cell–cell and cell–medium interactions are quantified by adhesion and cohesion energies. In a multicellular aggregate system with a fixed number of cells and fixed amount of hydrogel media, where the effect of cell differentiation, proliferation and death are tactically neglected, the interaction energy is primarily dictated by the interfacial energy between cell and cell as well as between cell and medium particles on the lattice, respectively, based on the differential adhesion hypothesis. By using the transition state theory to track the time evolution of the multicellular system while minimizing the interfacial energy, KMC is shown to be an efficient time-dependent simulation tool to study the evolution of the multicellular aggregate system. In this study, numerical experiments are presented to simulate fusion and cell sorting during the biofabrication process of vascular networks, in which the bio-constructs are fabricated via engineering designs. The results predict the feasibility of fabricating the vascular

In-silico analysis on biofabricating vascular networks using kinetic Monte Carlo simulations.

Science.gov (United States)

Sun, Yi; Yang, Xiaofeng; Wang, Qi

2014-03-01

We present a computational modeling approach to study the fusion of multicellular aggregate systems in a novel scaffold-less biofabrication process, known as 'bioprinting'. In this novel technology, live multicellular aggregates are used as fundamental building blocks to make tissues or organs (collectively known as the bio-constructs,) via the layer-by-layer deposition technique or other methods; the printed bio-constructs embedded in maturogens, consisting of nutrient-rich bio-compatible hydrogels, are then placed in bioreactors to undergo the cellular aggregate fusion process to form the desired functional bio-structures. Our approach reported here is an agent-based modeling method, which uses the kinetic Monte Carlo (KMC) algorithm to evolve the cellular system on a lattice. In this method, the cells and the hydrogel media, in which cells are embedded, are coarse-grained to material's points on a three-dimensional (3D) lattice, where the cell-cell and cell-medium interactions are quantified by adhesion and cohesion energies. In a multicellular aggregate system with a fixed number of cells and fixed amount of hydrogel media, where the effect of cell differentiation, proliferation and death are tactically neglected, the interaction energy is primarily dictated by the interfacial energy between cell and cell as well as between cell and medium particles on the lattice, respectively, based on the differential adhesion hypothesis. By using the transition state theory to track the time evolution of the multicellular system while minimizing the interfacial energy, KMC is shown to be an efficient time-dependent simulation tool to study the evolution of the multicellular aggregate system. In this study, numerical experiments are presented to simulate fusion and cell sorting during the biofabrication process of vascular networks, in which the bio-constructs are fabricated via engineering designs. The results predict the feasibility of fabricating the vascular structures

Magnesium prevents vascular calcification in vitro by inhibition of hydroxyapatite crystal formation.

NARCIS (Netherlands)

Braake, A.D. ter; Tinnemans, P.T.; Shanahan, C.M.; Hoenderop, J.G.J.; Baaij, J.H.F. de

2018-01-01

Magnesium has been shown to effectively prevent vascular calcification associated with chronic kidney disease. Magnesium has been hypothesized to prevent the upregulation of osteoblastic genes that potentially drives calcification. However, extracellular effects of magnesium on hydroxyapatite

Network centrality based team formation: A case study on T-20 cricket

Directory of Open Access Journals (Sweden)

Paramita Dey

2017-07-01

Full Text Available This paper proposes and evaluates the novel utilization of small world network properties for the formation of team of players with both best performances and best belongingness within the team network. To verify this concept, this methodology is applied to T-20 cricket teams. The players are treated as nodes of the network, whereas the number of interactions between team members is denoted as the edges between those nodes. All intra country networks form the cricket network for this case study. Analysis of the networks depicts that T-20 cricket network inherits all characteristics of small world network. Making a quantitative measure for an individual performance in the team sports is important with respect to the fact that for team selection of an International match, from pool of best players, only eleven players can be selected for the team. The statistical record of each player considered as a traditional way of quantifying the performance of a player. But the other criteria such as performing against a strong opponent or performance as an effective team member such as fielding, running between the wickets, good partnership deserves more credential. In this paper a revised method based on social networking is presented to quantify the quality of team belongingness and efficiency of each player. The application of Social Network Analysis (SNA is explored to measure performances and the rank of the players. A bidirectional weighted network of players is generated using the information collected from T-20 cricket (2014–2016 and used for network analysis. Thus team was formed based on that ranking and compared with their IPL (Indian Premier League performances of 2016.

Macrophage conditioned medium induced cellular network formation in MCF-7 cells through enhanced tunneling nanotube formation and tunneling nanotube mediated release of viable cytoplasmic fragments

International Nuclear Information System (INIS)

Patheja, Pooja; Sahu, Khageswar

2017-01-01

Infiltrating macrophages in tumor microenvironment, through their secreted cytokines and growth factors, regulate several processes of cancer progression such as cancer cell survival, proliferation, invasion, metastasis and angiogenesis. Recently, intercellular cytoplasmic bridges between cancer cells referred as tunneling nanotubes (TNTs) have been recognized as novel mode of intercellular communication between cancer cells. In this study, we investigated the effect of inflammatory mediators present in conditioned medium derived from macrophages on the formation of TNTs in breast adenocarcinoma cells MCF-7. Results show that treatment with macrophage conditioned medium (MφCM) not only enhanced TNT formation between cells but also stimulated the release of independently migrating viable cytoplasmic fragments, referred to as microplasts, from MCF-7 cells. Time lapse microscopy revealed that microplasts were released from parent cancer cells in extracellular space through formation of TNT-like structures. Mitochondria, vesicles and cytoplasm could be transferred from parent cell body to microplasts through connecting TNTs. The microplasts could also be resorbed into the parent cell body by retraction of the connecting TNTs. Microplast formation inhibited in presence cell migration inhibitor, cytochalasin-B. Notably by utilizing migratory machinery within microplasts, distantly located MCF-7 cells formed several TNT based intercellular connections, leading to formation of physically connected network of cells. Together, these results demonstrate novel role of TNTs in microplast formation, novel modes of TNT formation mediated by microplasts and stimulatory effect of MφCM on cellular network formation in MCF-7 cells mediated through enhanced TNT and microplast formation.

Macrophage conditioned medium induced cellular network formation in MCF-7 cells through enhanced tunneling nanotube formation and tunneling nanotube mediated release of viable cytoplasmic fragments

Energy Technology Data Exchange (ETDEWEB)

Patheja, Pooja, E-mail: pooja.patheja8@gmail.com [Laser Biomedical Applications Section, Raja Ramanna Centre for Advanced Technology, Indore 452013, Madhya Pradesh (India); Homi Bhabha National Institute, Training School Complex, Anushaktinagar, Mumbai 400094, Maharashtra (India); Sahu, Khageswar [Laser Biomedical Applications Section, Raja Ramanna Centre for Advanced Technology, Indore 452013, Madhya Pradesh (India)

2017-06-15

Infiltrating macrophages in tumor microenvironment, through their secreted cytokines and growth factors, regulate several processes of cancer progression such as cancer cell survival, proliferation, invasion, metastasis and angiogenesis. Recently, intercellular cytoplasmic bridges between cancer cells referred as tunneling nanotubes (TNTs) have been recognized as novel mode of intercellular communication between cancer cells. In this study, we investigated the effect of inflammatory mediators present in conditioned medium derived from macrophages on the formation of TNTs in breast adenocarcinoma cells MCF-7. Results show that treatment with macrophage conditioned medium (MφCM) not only enhanced TNT formation between cells but also stimulated the release of independently migrating viable cytoplasmic fragments, referred to as microplasts, from MCF-7 cells. Time lapse microscopy revealed that microplasts were released from parent cancer cells in extracellular space through formation of TNT-like structures. Mitochondria, vesicles and cytoplasm could be transferred from parent cell body to microplasts through connecting TNTs. The microplasts could also be resorbed into the parent cell body by retraction of the connecting TNTs. Microplast formation inhibited in presence cell migration inhibitor, cytochalasin-B. Notably by utilizing migratory machinery within microplasts, distantly located MCF-7 cells formed several TNT based intercellular connections, leading to formation of physically connected network of cells. Together, these results demonstrate novel role of TNTs in microplast formation, novel modes of TNT formation mediated by microplasts and stimulatory effect of MφCM on cellular network formation in MCF-7 cells mediated through enhanced TNT and microplast formation.

Downregulation of B-myb promotes senescence via the ROS-mediated p53/p21 pathway, in vascular endothelial cells.

Science.gov (United States)

Zhou, Zhihui; Yin, Yanlin; Chang, Qun; Sun, Guanqun; Lin, Jiahui; Dai, Yalei

2017-04-01

To reveal whether B-myb is involved in preventing senescence of vascular endothelial cells, and if so, to identify possible mechanisms for it. C57/BL6 male mice and primary human aortic endothelial cells (HAECs) were used. Bleomycin was applied to induce stress-related premature senescence. B-myb knockdown was achieved using an siRNA technique and cell senescence was assessed using the senescence-associated β-galactosidase (SA-β-gal) assay. Intracellular reactive oxygen species (ROS) production was analysed using an ROS assay kit and cell proliferation was evaluated using KFluor488 EdU kit. Capillary tube network formation was determined by Matrigel assay. Expressions of mRNA and protein levels were detected by real-time PCR and western blotting. B-myb expression significantly decreased, while p53 and p21 expressions increased in the aortas of aged mice. This expression pattern was also found in replicative senescent HAECs and senescent HAECs induced by bleomycin. B-myb knockdown resulted in upregulation of p22 phox , ROS accumulation and cell senescence of HAECs. Downregulation of B-myb significantly inhibited cell proliferation and capillary tube network formation and activated the p53/p21 signalling pathway. Blocking ROS production or inhibiting p53 activation remarkably attenuated SA-β-gal activity and delayed cell senescence induced by B-myb-silencing. Downregulation of B-myb induced senescence by upregulation of p22 phox and activation of the ROS/p53/p21 pathway, in our vascular endothelial cells, suggesting that B-myb may be a novel candidate for regulating cell senescence to protect against endothelial senescence-related cardiovascular diseases. © 2016 John Wiley & Sons Ltd.

Endothelial cell motility, coordination and pattern formation during vasculogenesis.

Science.gov (United States)

Czirok, Andras

2013-01-01

How vascular networks assemble is a fundamental problem of developmental biology that also has medical importance. To explain the organizational principles behind vascular patterning, we must understand how can tissue level structures be controlled through cell behavior patterns like motility and adhesion that, in turn, are determined by biochemical signal transduction processes? We discuss the various ideas that have been proposed as mechanisms for vascular network assembly: cell motility guided by extracellular matrix alignment (contact guidance), chemotaxis guided by paracrine and autocrine morphogens, and multicellular sprouting guided by cell-cell contacts. All of these processes yield emergent patterns, thus endothelial cells can form an interconnected structure autonomously, without guidance from an external pre-pattern. © 2013 Wiley Periodicals, Inc.

Key role of microRNA-15a in the KLF4 suppressions of proliferation and angiogenesis in endothelial and vascular smooth muscle cells

International Nuclear Information System (INIS)

Zheng, Xuemei; Li, Aiqin; Zhao, Liang; Zhou, Tengfei; Shen, Qiang; Cui, Qinghua; Qin, Xiaomei

2013-01-01

Highlights: •This is the first demonstration that miR-15a is a novel target gene of KLF4. •A novel finding that KLF4 increases the expression of miR-15a in ECs and VSMCs. •The novel mechanism is that KLF4 inhibits the proliferation of ECs via miR-15a. •The novel mechanism is that KLF4 inhibits the proliferation of VSMCs via miR-15. •miR-15a mediates the anti-angiogenic activity of KLF4. -- Abstract: While recent insights indicate that the transcription factor Krüppel-like factor 4 (KLF4) is indispensable for vascular homeostasis, its exact role in proliferation and angiogenesis and how it functions remain unresolved. Thus, the aim of the present study was to evaluate the role of KLF4 in the proliferations of endothelial and vascular smooth muscle cells, as well as the angiogenesis. The overexpression of KLF4 in endothelial cells significantly impaired tube formation. KLF4 inhibited the formation of a vascular network in implanted Matrigel plugs in nude mice. Importantly, we found that KLF4 significantly upregulated the miR-15a expression in endothelial cells and vascular smooth muscle cells, and conversely, KLF4 depletion reduced the amount of miR-15a. Furthermore, KLF4 blocked cell cycle progression and decreased cyclin D1 expression in endothelial cells and vascular smooth muscle cells through the induction of miR-15a. Intriguingly, the delivery of a miR-15a antagomir to nude mice resulted in marked attenuation of the anti-angiogenic effect of KLF4. Collectively, our present study provide the first evidence that miR-15a as a direct transcriptional target of KLF4 that mediates the anti-proliferative and anti-angiogenic actions of KLF4, which indicates that KLF4 upregulation of miR-15a may represent a therapeutic option to suppress proliferative vascular disorders

Key role of microRNA-15a in the KLF4 suppressions of proliferation and angiogenesis in endothelial and vascular smooth muscle cells

Energy Technology Data Exchange (ETDEWEB)

Zheng, Xuemei; Li, Aiqin; Zhao, Liang; Zhou, Tengfei; Shen, Qiang [Institute of Cardiovascular Science, Peking University Health Science Center, Beijing 100191 (China); Key Laboratory of Molecular Cardiovascular Science of Ministry of Education, Peking University Health Science Center, Beijing 100191 (China); Cui, Qinghua [Department of Biomedical Informatics, Peking University Health Science Center, Beijing 100191 (China); Key Laboratory of Molecular Cardiovascular Science of Ministry of Education, Peking University Health Science Center, Beijing 100191 (China); Qin, Xiaomei, E-mail: xmqin@bjmu.edu.cn [Institute of Cardiovascular Science, Peking University Health Science Center, Beijing 100191 (China); Key Laboratory of Molecular Cardiovascular Science of Ministry of Education, Peking University Health Science Center, Beijing 100191 (China)

2013-08-09

Highlights: •This is the first demonstration that miR-15a is a novel target gene of KLF4. •A novel finding that KLF4 increases the expression of miR-15a in ECs and VSMCs. •The novel mechanism is that KLF4 inhibits the proliferation of ECs via miR-15a. •The novel mechanism is that KLF4 inhibits the proliferation of VSMCs via miR-15. •miR-15a mediates the anti-angiogenic activity of KLF4. -- Abstract: While recent insights indicate that the transcription factor Krüppel-like factor 4 (KLF4) is indispensable for vascular homeostasis, its exact role in proliferation and angiogenesis and how it functions remain unresolved. Thus, the aim of the present study was to evaluate the role of KLF4 in the proliferations of endothelial and vascular smooth muscle cells, as well as the angiogenesis. The overexpression of KLF4 in endothelial cells significantly impaired tube formation. KLF4 inhibited the formation of a vascular network in implanted Matrigel plugs in nude mice. Importantly, we found that KLF4 significantly upregulated the miR-15a expression in endothelial cells and vascular smooth muscle cells, and conversely, KLF4 depletion reduced the amount of miR-15a. Furthermore, KLF4 blocked cell cycle progression and decreased cyclin D1 expression in endothelial cells and vascular smooth muscle cells through the induction of miR-15a. Intriguingly, the delivery of a miR-15a antagomir to nude mice resulted in marked attenuation of the anti-angiogenic effect of KLF4. Collectively, our present study provide the first evidence that miR-15a as a direct transcriptional target of KLF4 that mediates the anti-proliferative and anti-angiogenic actions of KLF4, which indicates that KLF4 upregulation of miR-15a may represent a therapeutic option to suppress proliferative vascular disorders.

Distinctive Resting State Network Disruptions Among Alzheimer's Disease, Subcortical Vascular Dementia, and Mixed Dementia Patients.

Science.gov (United States)

Kim, Hee Jin; Cha, Jungho; Lee, Jong-Min; Shin, Ji Soo; Jung, Na-Yeon; Kim, Yeo Jin; Choe, Yearn Seong; Lee, Kyung Han; Kim, Sung Tae; Kim, Jae Seung; Lee, Jae Hong; Na, Duk L; Seo, Sang Won

2016-01-01

Recent advances in resting-state functional MRI have revealed altered functional networks in Alzheimer's disease (AD), especially those of the default mode network (DMN) and central executive network (CEN). However, few studies have evaluated whether small vessel disease (SVD) or combined amyloid and SVD burdens affect the DMN or CEN. The aim of this study was to evaluate whether SVD or combined amyloid and SVD burdens affect the DMN or CEN. In this cross-sectional study, we investigated the resting-state functional connectivity within DMN and CEN in 37 Pittsburgh compound-B (PiB)(+) AD, 37 PiB(-) subcortical vascular dementia (SVaD), 13 mixed dementia patients, and 65 normal controls. When the resting-state DMN of PiB(+) AD and PiB(-) SVaD patients were compared, the PiB(+) AD patients displayed lower functional connectivity in the inferior parietal lobule while the PiB(-) SVaD patients displayed lower functional connectivity in the medial frontal and superior frontal gyri. Compared to the PiB(-) SVaD or PiB(+) AD, the mixed dementia patients displayed lower functional connectivity within the DMN in the posterior cingulate gyrus. When the resting-state CEN connectivity of PiB(+) AD and PiB(-) SVaD patients were compared, the PiB(-) SVaD patients displayed lower functional connectivity in the anterior insular region. Compared to the PiB(-) SVaD or PiB(+) AD, the mixed dementia patients displayed lower functional connectivity within the CEN in the inferior frontal gyrus. Our findings suggest that in PiB(+) AD and PiB(-) SVaD, there is divergent disruptions in resting-state DMN and CEN. Furthermore, patients with combined amyloid and SVD burdens exhibited more disrupted resting-state DMN and CEN than patients with only amyloid or SVD burden.

Unravelling the secret of seed-based gels in water: the nanoscale 3D network formation.

Science.gov (United States)

Samateh, Malick; Pottackal, Neethu; Manafirasi, Setareh; Vidyasagar, Adiyala; Maldarelli, Charles; John, George

2018-05-09

Chia (Salvia hispanica) and basil (Ocimum basilicum) seeds have the intrinsic ability to form a hydrogel concomitant with moisture-retention, slow releasing capability and proposed health benefits such as curbing diabetes and obesity by delaying digestion process. However, the underlying mode of gelation at nanoscopic level is not clearly explained or explored. The present study elucidates and corroborates the hypothesis that the gelling behavior of such seeds is due to their nanoscale 3D-network formation. The preliminary study revealed the influence of several conditions like polarity, pH and hydrophilicity/hydrophobicity on fiber extrusion from the seeds which leads to gelation. Optical microscopic analysis clearly demonstrated bundles of fibers emanating from the seed coat while in contact with water, and live growth of fibers to form 3D network. Scanning electron microscope (SEM) and transmission electron microscope (TEM) studies confirmed 3D network formation with fiber diameters ranging from 20 to 50 nm.

A new building block for DNA network formation by self-assembly and polymerase chain reaction.

Science.gov (United States)

Bußkamp, Holger; Keller, Sascha; Robotta, Marta; Drescher, Malte; Marx, Andreas

2014-01-01

The predictability of DNA self-assembly is exploited in many nanotechnological approaches. Inspired by naturally existing self-assembled DNA architectures, branched DNA has been developed that allows self-assembly to predesigned architectures with dimensions on the nanometer scale. DNA is an attractive material for generation of nanostructures due to a plethora of enzymes which modify DNA with high accuracy, providing a toolbox for many different manipulations to construct nanometer scaled objects. We present a straightforward synthesis of a rigid DNA branching building block successfully used for the generation of DNA networks by self-assembly and network formation by enzymatic DNA synthesis. The Y-shaped 3-armed DNA construct, bearing 3 primer strands is accepted by Taq DNA polymerase. The enzyme uses each arm as primer strand and incorporates the branched construct into large assemblies during PCR. The networks were investigated by agarose gel electrophoresis, atomic force microscopy, dynamic light scattering, and electron paramagnetic resonance spectroscopy. The findings indicate that rather rigid DNA networks were formed. This presents a new bottom-up approach for DNA material formation and might find applications like in the generation of functional hydrogels.

Prediction of Austenite Formation Temperatures Using Artificial Neural Networks

International Nuclear Information System (INIS)

Schulze, P; Schmidl, E; Grund, T; Lampke, T

2016-01-01

For the modeling and design of heat treatments, in consideration of the development/ transformation of the microstructure, different material data depending on the chemical composition, the respective microstructure/phases and the temperature are necessary. Material data are, e.g. the thermal conductivity, heat capacity, thermal expansion and transformation data etc. The quality of thermal simulations strongly depends on the accuracy of the material data. For many materials, the required data - in particular for different microstructures and temperatures - are rare in the literature. In addition, a different chemical composition within the permitted limits of the considered steel alloy cannot be predicted. A solution for this problem is provided by the calculation of material data using Artificial Neural Networks (ANN). In the present study, the start and finish temperatures of the transformation from the bcc lattice to the fcc lattice structure of hypoeutectoid steels are calculated using an Artificial Neural Network. An appropriate database containing different transformation temperatures (austenite formation temperatures) to train the ANN is selected from the literature. In order to find a suitable feedforward network, the network topologies as well as the activation functions of the hidden layers are varied and subsequently evaluated in terms of the prediction accuracy. The transformation temperatures calculated by the ANN exhibit a very good compliance compared to the experimental data. The results show that the prediction performance is even higher compared to classical empirical equations such as Andrews or Brandis. Therefore, it can be assumed that the presented ANN is a convenient tool to distinguish between bcc and fcc phases in hypoeutectoid steels. (paper)

Prediction of Austenite Formation Temperatures Using Artificial Neural Networks

Science.gov (United States)

Schulze, P.; Schmidl, E.; Grund, T.; Lampke, T.

2016-03-01

For the modeling and design of heat treatments, in consideration of the development/ transformation of the microstructure, different material data depending on the chemical composition, the respective microstructure/phases and the temperature are necessary. Material data are, e.g. the thermal conductivity, heat capacity, thermal expansion and transformation data etc. The quality of thermal simulations strongly depends on the accuracy of the material data. For many materials, the required data - in particular for different microstructures and temperatures - are rare in the literature. In addition, a different chemical composition within the permitted limits of the considered steel alloy cannot be predicted. A solution for this problem is provided by the calculation of material data using Artificial Neural Networks (ANN). In the present study, the start and finish temperatures of the transformation from the bcc lattice to the fcc lattice structure of hypoeutectoid steels are calculated using an Artificial Neural Network. An appropriate database containing different transformation temperatures (austenite formation temperatures) to train the ANN is selected from the literature. In order to find a suitable feedforward network, the network topologies as well as the activation functions of the hidden layers are varied and subsequently evaluated in terms of the prediction accuracy. The transformation temperatures calculated by the ANN exhibit a very good compliance compared to the experimental data. The results show that the prediction performance is even higher compared to classical empirical equations such as Andrews or Brandis. Therefore, it can be assumed that the presented ANN is a convenient tool to distinguish between bcc and fcc phases in hypoeutectoid steels.

Joint OSNR monitoring and modulation format identification in digital coherent receivers using deep neural networks.

Science.gov (United States)

Khan, Faisal Nadeem; Zhong, Kangping; Zhou, Xian; Al-Arashi, Waled Hussein; Yu, Changyuan; Lu, Chao; Lau, Alan Pak Tao

2017-07-24

We experimentally demonstrate the use of deep neural networks (DNNs) in combination with signals' amplitude histograms (AHs) for simultaneous optical signal-to-noise ratio (OSNR) monitoring and modulation format identification (MFI) in digital coherent receivers. The proposed technique automatically extracts OSNR and modulation format dependent features of AHs, obtained after constant modulus algorithm (CMA) equalization, and exploits them for the joint estimation of these parameters. Experimental results for 112 Gbps polarization-multiplexed (PM) quadrature phase-shift keying (QPSK), 112 Gbps PM 16 quadrature amplitude modulation (16-QAM), and 240 Gbps PM 64-QAM signals demonstrate OSNR monitoring with mean estimation errors of 1.2 dB, 0.4 dB, and 1 dB, respectively. Similarly, the results for MFI show 100% identification accuracy for all three modulation formats. The proposed technique applies deep machine learning algorithms inside standard digital coherent receiver and does not require any additional hardware. Therefore, it is attractive for cost-effective multi-parameter estimation in next-generation elastic optical networks (EONs).

Opinion formation and distribution in a bounded-confidence model on various networks

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Meng, X. Flora; Van Gorder, Robert A.; Porter, Mason A.

2018-02-01

In the social, behavioral, and economic sciences, it is important to predict which individual opinions eventually dominate in a large population, whether there will be a consensus, and how long it takes for a consensus to form. Such ideas have been studied heavily both in physics and in other disciplines, and the answers depend strongly both on how one models opinions and on the network structure on which opinions evolve. One model that was created to study consensus formation quantitatively is the Deffuant model, in which the opinion distribution of a population evolves via sequential random pairwise encounters. To consider heterogeneity of interactions in a population along with social influence, we study the Deffuant model on various network structures (deterministic synthetic networks, random synthetic networks, and social networks constructed from Facebook data). We numerically simulate the Deffuant model and conduct regression analyses to investigate the dependence of the time to reach steady states on various model parameters, including a confidence bound for opinion updates, the number of participating entities, and their willingness to compromise. We find that network structure and parameter values both have important effects on the convergence time and the number of steady-state opinion groups. For some network architectures, we observe that the relationship between the convergence time and model parameters undergoes a transition at a critical value of the confidence bound. For some networks, the steady-state opinion distribution also changes from consensus to multiple opinion groups at this critical value.

Functional organization of the vascular network of Physarum polycephalum

International Nuclear Information System (INIS)

Baumgarten, Werner; Hauser, Marcus J B

2013-01-01

The plasmodium of the slime mould Physarum polycephalum forms a transportation network of veins, in which protoplasm is transported due to peristaltic pumping. This network forms a planar, weighted, undirected graph that, for the first time, can be extracted automatically from photographs or movies. Thus, data from real transportation networks have now become available for the investigation of network properties. We determine the local drag of the vein segments and use these data to calculate the transport efficiency. We unravel which veins form the backbone of the transportation network by using a centrality measure from graph theory. The principal vein segments lie on relatively ample cycles of veins, and the most important segments are those that belong simultaneously to two of these principal cycles. Each principal cycle contains a series of smaller cycles of veins of lower transport efficiency, thus reflecting the hierarchical and self-similar structure of the transportation network. Finally, we calculate accessibility maps that show how easily different nodes of the network may be reached from a given reference node. (paper)

Integration of Self-Assembled Microvascular Networks with Microfabricated PEG-Based Hydrogels.

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Cuchiara, Michael P; Gould, Daniel J; McHale, Melissa K; Dickinson, Mary E; West, Jennifer L

2012-11-07

Despite tremendous efforts, tissue engineered constructs are restricted to thin, simple tissues sustained only by diffusion. The most significant barrier in tissue engineering is insufficient vascularization to deliver nutrients and metabolites during development in vitro and to facilitate rapid vascular integration in vivo. Tissue engineered constructs can be greatly improved by developing perfusable microvascular networks in vitro in order to provide transport that mimics native vascular organization and function. Here a microfluidic hydrogel is integrated with a self-assembling pro-vasculogenic co-culture in a strategy to perfuse microvascular networks in vitro. This approach allows for control over microvascular network self-assembly and employs an anastomotic interface for integration of self-assembled micro-vascular networks with fabricated microchannels. As a result, transport within the system shifts from simple diffusion to vessel supported convective transport and extra-vessel diffusion, thus improving overall mass transport properties. This work impacts the development of perfusable prevascularized tissues in vitro and ultimately tissue engineering applications in vivo.

The skeletal vascular system - Breathing life into bone tissue.

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Stegen, Steve; Carmeliet, Geert

2017-08-26

During bone development, homeostasis and repair, a dense vascular system provides oxygen and nutrients to highly anabolic skeletal cells. Characteristic for the vascular system in bone is the serial organization of two capillary systems, each typified by specific morphological and physiological features. Especially the arterial capillaries mediate the growth of the bone vascular system, serve as a niche for skeletal and hematopoietic progenitors and couple angiogenesis to osteogenesis. Endothelial cells and osteoprogenitor cells interact not only physically, but also communicate to each other by secretion of growth factors. A vital angiogenic growth factor is vascular endothelial growth factor and its expression in skeletal cells is controlled by osteogenic transcription factors and hypoxia signaling, whereas the secretion of angiocrine factors by endothelial cells is regulated by Notch signaling, blood flow and possibly hypoxia. Bone loss and impaired fracture repair are often associated with reduced and disorganized blood vessel network and therapeutic targeting of the angiogenic response may contribute to enhanced bone regeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

Vascular endothelial growth factor-A determines detectability of experimental melanoma brain metastasis in GD-DTPA-enhanced MRI.

NARCIS (Netherlands)

Leenders, W.P.J.; Kusters, B.; Pikkemaat, J.A.; Wesseling, P.; Ruiter, D.J.; Heerschap, A.; Barentsz, J.O.; Waal, R.M.W. de

2003-01-01

We have previously shown that the dense vascular network in mouse brain allows for growth of human melanoma xenografts (Mel57) by co-option of preexisting vessels. Overexpression of recombinant vascular endothelial growth factor-A (VEGF-A) by such xenografts induced functional and morphologic

Macrophage conditioned medium induced cellular network formation in MCF-7 cells through enhanced tunneling nanotube formation and tunneling nanotube mediated release of viable cytoplasmic fragments.

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Patheja, Pooja; Sahu, Khageswar

2017-06-15

Infiltrating macrophages in tumor microenvironment, through their secreted cytokines and growth factors, regulate several processes of cancer progression such as cancer cell survival, proliferation, invasion, metastasis and angiogenesis. Recently, intercellular cytoplasmic bridges between cancer cells referred as tunneling nanotubes (TNTs) have been recognized as novel mode of intercellular communication between cancer cells. In this study, we investigated the effect of inflammatory mediators present in conditioned medium derived from macrophages on the formation of TNTs in breast adenocarcinoma cells MCF-7. Results show that treatment with macrophage conditioned medium (MɸCM) not only enhanced TNT formation between cells but also stimulated the release of independently migrating viable cytoplasmic fragments, referred to as microplasts, from MCF-7 cells. Time lapse microscopy revealed that microplasts were released from parent cancer cells in extracellular space through formation of TNT-like structures. Mitochondria, vesicles and cytoplasm could be transferred from parent cell body to microplasts through connecting TNTs. The microplasts could also be resorbed into the parent cell body by retraction of the connecting TNTs. Microplast formation inhibited in presence cell migration inhibitor, cytochalasin-B. Notably by utilizing migratory machinery within microplasts, distantly located MCF-7 cells formed several TNT based intercellular connections, leading to formation of physically connected network of cells. Together, these results demonstrate novel role of TNTs in microplast formation, novel modes of TNT formation mediated by microplasts and stimulatory effect of MɸCM on cellular network formation in MCF-7 cells mediated through enhanced TNT and microplast formation. Copyright © 2017 Elsevier Inc. All rights reserved.

Vascular quality of care pilot study: how admission to a vascular surgery service affects evidence-based pharmacologic risk factor modification in patients with lower extremity peripheral arterial disease

Directory of Open Access Journals (Sweden)

Steenhof N

2014-06-01

Full Text Available Naomi Steenhof,1,2 Francesca Le Piane,1 Kori Leblanc,1–3 Naomi R Eisenberg,4 Yvonne Kwan,1 Christine Malmberg,1,6 Alexandra Papadopoulos,5,7 Graham Roche-Nagle4,7,8 1Department of Pharmacy, University Health Network, 2Leslie Dan Faculty of Pharmacy, University of Toronto, 3Centre for Innovation in Complex Care, University Health Network, 4Division of Vascular Surgery, University Health Network, 5Faculty of Nursing, University of Toronto, Toronto, ON, 6Victoria General Hospital, Vancouver Island Health Authority, Victoria, BC, 7Peter Munk Cardiac Centre, University Health Network, 8Faculty of Medicine, University of Toronto, Toronto, ON, Canada Background: Peripheral arterial disease (PAD guidelines recommend aggressive risk factor modification to improve cardiovascular outcomes. Recommended pharmacologic therapies include antiplatelets, angiotensin converting enzyme (ACE inhibitors, and HMG-CoA-reductase inhibitors (statins. Purpose: We studied the degree to which patient admission to a vascular surgery service increased the use of these therapies. Patients and methods: The authors conducted a retrospective chart review of 150 patients with PAD admitted to the vascular surgery service at a large Canadian tertiary care hospital. The use of recommended pharmacologic therapies at the time of admission and discharge were compared. A multidisciplinary clinical team established criteria by which patients were deemed ineligible to receive any of the recommended therapies. Angiotensin receptor blockers (ARBs were considered an alternative to ACE inhibitors. Results: Prior to hospital admission, 64% of patients were on antiplatelet therapy, 67% were on an ACE inhibitor or ARB, and 71% were on a statin. At the time of discharge, 91% of patients were on an antiplatelet (or not, with an acceptable reason, 77% were on an ACE inhibitor or an ARB (or not, with an acceptable reason, and 85% were on a statin (or not, with an acceptable reason. While new

Alliance group formation: enabling and constraining effects of embeddedness and social capital in strategic technology alliance networks

NARCIS (Netherlands)

Duysters, G.M.; Lemmens, C.E.A.V.

2003-01-01

The role of embeddedness and social capital in the process of alliance group formation in strategic technology alliance networks is examined. In particular, the social mechanisms that enable and enforce alliance group formation is studies. It is argued that the enabling effect of embeddedness during

Tolerance-based interaction: a new model targeting opinion formation and diffusion in social networks

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Alexandru Topirceanu

2016-01-01

Full Text Available One of the main motivations behind social network analysis is the quest for understanding opinion formation and diffusion. Previous models have limitations, as they typically assume opinion interaction mechanisms based on thresholds which are either fixed or evolve according to a random process that is external to the social agent. Indeed, our empirical analysis on large real-world datasets such as Twitter, Meme Tracker, and Yelp, uncovers previously unaccounted for dynamic phenomena at population-level, namely the existence of distinct opinion formation phases and social balancing. We also reveal that a phase transition from an erratic behavior to social balancing can be triggered by network topology and by the ratio of opinion sources. Consequently, in order to build a model that properly accounts for these phenomena, we propose a new (individual-level opinion interaction model based on tolerance. As opposed to the existing opinion interaction models, the new tolerance model assumes that individual’s inner willingness to accept new opinions evolves over time according to basic human traits. Finally, by employing discrete event simulation on diverse social network topologies, we validate our opinion interaction model and show that, although the network size and opinion source ratio are important, the phase transition to social balancing is mainly fostered by the democratic structure of the small-world topology.

Major Vascular Neurocognitive Disorder: A Reappraisal to Vascular Dementia

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Emre Kumral

2017-03-01

Full Text Available Major vascular neurocognitive disorder (NCD is the second leading form of dementia after Alzheimer’s disease, accounting for 17-20% of all dementias. Vascular NCD is a progressive disease caused by reduced cerebral blood flow related to multiple large volume or lacunar infarcts that induce a sudden onset and stepwise decline in cognitive abilities. Despite its prevalence and clinical importance, there is still controversy in the terminology of vascular NCD. Only after the release of Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5 (2013 did the American Psychiatric Association define vascular dementia as “major vascular NCD”. This review includes an overview of risk factors, pathophysiology, types, diagnostic and clinical features of major vascular NCD, and current treatment options of vascular NCD regarding to DSM-5 criteria

Endothelial Dll4 overexpression reduces vascular response and inhibits tumor growth and metastasization in vivo.

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Trindade, Alexandre; Djokovic, Dusan; Gigante, Joana; Mendonça, Liliana; Duarte, António

2017-03-14

The inhibition of Delta-like 4 (Dll4)/Notch signaling has been shown to result in excessive, nonfunctional vessel proliferation and significant tumor growth suppression. However, safety concerns emerged with the identification of side effects resulting from chronic Dll4/Notch blockade. Alternatively, we explored the endothelial Dll4 overexpression using different mouse tumor models. We used a transgenic mouse model of endothelial-specific Dll4 overexpression, previously produced. Growth kinetics and vascular histopathology of several types of solid tumors was evaluated, namely Lewis Lung Carcinoma xenografts, chemically-induced skin papillomas and RIP1-Tag2 insulinomas. We found that increased Dll4/Notch signaling reduces tumor growth by reducing vascular endothelial growth factor (VEGF)-induced endothelial proliferation, tumor vessel density and overall tumor blood supply. In addition, Dll4 overexpression consistently improved tumor vascular maturation and functionality, as indicated by increased vessel calibers, enhanced mural cell recruitment and increased network perfusion. Importantly, the tumor vessel normalization is not more effective than restricted vessel proliferation, but was found to prevent metastasis formation and allow for increased delivery to the tumor of concomitant chemotherapy, improving its efficacy. By reducing endothelial sensitivity to VEGF, these results imply that Dll4/Notch stimulation in tumor microenvironment could be beneficial to solid cancer patient treatment by reducing primary tumor size, improving tumor drug delivery and reducing metastization. Endothelial specific Dll4 overexpression thus appears as a promising anti-angiogenic modality that might improve cancer control.

Comparative genomics reveals conservative evolution of the xylem transcriptome in vascular plants.

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Li, Xinguo; Wu, Harry X; Southerton, Simon G

2010-06-21

Wood is a valuable natural resource and a major carbon sink. Wood formation is an important developmental process in vascular plants which played a crucial role in plant evolution. Although genes involved in xylem formation have been investigated, the molecular mechanisms of xylem evolution are not well understood. We use comparative genomics to examine evolution of the xylem transcriptome to gain insights into xylem evolution. The xylem transcriptome is highly conserved in conifers, but considerably divergent in angiosperms. The functional domains of genes in the xylem transcriptome are moderately to highly conserved in vascular plants, suggesting the existence of a common ancestral xylem transcriptome. Compared to the total transcriptome derived from a range of tissues, the xylem transcriptome is relatively conserved in vascular plants. Of the xylem transcriptome, cell wall genes, ancestral xylem genes, known proteins and transcription factors are relatively more conserved in vascular plants. A total of 527 putative xylem orthologs were identified, which are unevenly distributed across the Arabidopsis chromosomes with eight hot spots observed. Phylogenetic analysis revealed that evolution of the xylem transcriptome has paralleled plant evolution. We also identified 274 conifer-specific xylem unigenes, all of which are of unknown function. These xylem orthologs and conifer-specific unigenes are likely to have played a crucial role in xylem evolution. Conifers have highly conserved xylem transcriptomes, while angiosperm xylem transcriptomes are relatively diversified. Vascular plants share a common ancestral xylem transcriptome. The xylem transcriptomes of vascular plants are more conserved than the total transcriptomes. Evolution of the xylem transcriptome has largely followed the trend of plant evolution.

Sida rhomboidea.Roxb aqueous extract down-regulates in vivo expression of vascular cell adhesion molecules in atherogenic rats and inhibits in vitro macrophage differentiation and foam cell formation.

Science.gov (United States)

Thounaojam, Menaka C; Jadeja, Ravirajsinh N; Salunke, Sunita P; Devkar, Ranjitsinh V; Ramachandran, A V

2012-10-01

The present study evaluates efficacy of Sida rhomboidea.Roxb (SR) leaves extract in ameliorating experimental atherosclerosis using in vitro and in vivo experimental models. Atherogenic (ATH) diet fed rats recorded significant increment in the serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), very LDL (VLDL), autoantibody against oxidized LDL (Ox-LDL), markers of LDL oxidation and decrement in high-density lipoprotein (HDL) along with increment in aortic TC and TG. The ex vivo LDL oxidation assay revealed an increased susceptibility of LDL isolated from ATH rats to undergo copper mediated oxidation. These set of changes were minimized by simultaneous co-supplementation of SR extract to ATH diet fed rats. Histopathology of aorta and immunolocalization studies recorded pronounced atheromatous plaque formation, vascular calcification, significant elastin derangements and higher expression of macrophage surface marker (F4/80), vascular cell adhesion molecule-1 (VCAM-1) and p-selectin in ATH rats. Whereas, ATH+SR rats depicted minimal evidence of atheromatous plaque formation, calcium deposition, distortion/defragmentation of elastin and accumulation of macrophages along with lowered expression of VCAM-1 and P-selectin compared to ATH rats. Further, monocyte to macrophage differentiation and in vitro foam cell formation were significantly attenuated in presence of SR extract. In conclusion, SR extract has the potency of controlling experimental atherosclerosis and can be used as promising herbal supplement in combating atherosclerosis.

Brain vascular image segmentation based on fuzzy local information C-means clustering

Science.gov (United States)

Hu, Chaoen; Liu, Xia; Liang, Xiao; Hui, Hui; Yang, Xin; Tian, Jie

2017-02-01

Light sheet fluorescence microscopy (LSFM) is a powerful optical resolution fluorescence microscopy technique which enables to observe the mouse brain vascular network in cellular resolution. However, micro-vessel structures are intensity inhomogeneity in LSFM images, which make an inconvenience for extracting line structures. In this work, we developed a vascular image segmentation method by enhancing vessel details which should be useful for estimating statistics like micro-vessel density. Since the eigenvalues of hessian matrix and its sign describes different geometric structure in images, which enable to construct vascular similarity function and enhance line signals, the main idea of our method is to cluster the pixel values of the enhanced image. Our method contained three steps: 1) calculate the multiscale gradients and the differences between eigenvalues of Hessian matrix. 2) In order to generate the enhanced microvessels structures, a feed forward neural network was trained by 2.26 million pixels for dealing with the correlations between multi-scale gradients and the differences between eigenvalues. 3) The fuzzy local information c-means clustering (FLICM) was used to cluster the pixel values in enhance line signals. To verify the feasibility and effectiveness of this method, mouse brain vascular images have been acquired by a commercial light-sheet microscope in our lab. The experiment of the segmentation method showed that dice similarity coefficient can reach up to 85%. The results illustrated that our approach extracting line structures of blood vessels dramatically improves the vascular image and enable to accurately extract blood vessels in LSFM images.

Perturbing phosphoinositide homeostasis oppositely affects vascular differentiation in Arabidopsis thaliana roots

NARCIS (Netherlands)

Gujas, Bojan; Cruz, Tiago M D; Kastanaki, Elizabeth; Vermeer, Joop E M; Munnik, Teun; Rodriguez-Villalon, Antia

2017-01-01

The plant vascular network consists of specialized phloem and xylem elements that undergo two distinct morphogenetic developmental programs to become transport-functional units. Whereas vacuolar rupture is a determinant step in protoxylem differentiation, protophloem elements never form a big

Hyperglycemia-Induced Modulation of the Physiognomy and Angiogenic Potential of Fibroblasts Mediated by Matrix Metalloproteinase-2: Implications for Venous Stenosis Formation Associated with Hemodialysis Vascular Access in Diabetic Milieu.

Science.gov (United States)

Janardhanan, Rajiv; Kilari, Sreenivasulu; Leof, Edward B; Misra, Sanjay

2015-01-01

It is hypothesized that venous stenosis formation associated with hemodialysis vascular-access failure is caused by hypoxia-mediated fibroblast-to-myofibroblast differentiation accompanied by proliferation and migration, and that diabetic patients have worse clinical outcomes. The aim of this study was to determine the functional and gene expression outcomes of matrix metalloproteinase-2 (Mmp-2) silencing in fibroblasts cultured under hyperglycemia and euglycemia with hypoxic and normoxic stimuli. AKR-2B fibroblasts were stably transduced using lentivirus-mediated shRNA-Mmp-2 or scrambled controls and subjected to hypoxia or normoxia under hyperglycemic or euglycemic conditions for 24 and 72 h. Gene expression of vascular endothelial growth factor-A (Vegf-A), Vegfr-1, Mmp-2, Mmp-9 and tissue inhibitors of matrix metalloproteinases (Timps) were determined by RT-PCR. Collagen I and IV secretion and cellular proliferation and migration were determined. Under hyperglycemic conditions, there is a significant reduction in the average gene expression of Vegf-A and Mmp-9, with an increase in Timp-1 at 24 h of hypoxia (p < 0.05) in Mmp-2-silenced fibroblasts when compared to controls. In addition, there is a decrease in collagen I and IV secretion and cellular migration. The euglycemic cells were able to reverse these findings. These findings demonstrate the rationale for using anti-Mmp-2 therapy in dialysis patients with hemodialysis vascular access in helping to reduce stenosis formation. © 2016 The Author(s) Published by S. Karger AG, Basel.

Additive Manufacturing of Vascular Grafts and Vascularized Tissue Constructs.

Science.gov (United States)

Elomaa, Laura; Yang, Yunzhi Peter

2017-10-01

There is a great need for engineered vascular grafts among patients with cardiovascular diseases who are in need of bypass therapy and lack autologous healthy blood vessels. In addition, because of the severe worldwide shortage of organ donors, there is an increasing need for engineered vascularized tissue constructs as an alternative to organ transplants. Additive manufacturing (AM) offers great advantages and flexibility of fabrication of cell-laden, multimaterial, and anatomically shaped vascular grafts and vascularized tissue constructs. Various inkjet-, extrusion-, and photocrosslinking-based AM techniques have been applied to the fabrication of both self-standing vascular grafts and porous, vascularized tissue constructs. This review discusses the state-of-the-art research on the use of AM for vascular applications and the key criteria for biomaterials in the AM of both acellular and cellular constructs. We envision that new smart printing materials that can adapt to their environment and encourage rapid endothelialization and remodeling will be the key factor in the future for the successful AM of personalized and dynamic vascular tissue applications.

Trends in lignin modification: a comprehensive analysis of the effects of genetic manipulations/mutations on lignification and vascular integrity

Science.gov (United States)

Anterola, Aldwin M.; Lewis, Norman G.

2002-01-01

A comprehensive assessment of lignin configuration in transgenic and mutant plants is long overdue. This review thus undertook the systematic analysis of trends manifested through genetic and mutational manipulations of the various steps associated with monolignol biosynthesis; this included consideration of the downstream effects on organized lignin assembly in the various cell types, on vascular function/integrity, and on plant growth and development. As previously noted for dirigent protein (homologs), distinct and sophisticated monolignol forming metabolic networks were operative in various cell types, tissues and organs, and form the cell-specific guaiacyl (G) and guaiacyl-syringyl (G-S) enriched lignin biopolymers, respectively. Regardless of cell type undergoing lignification, carbon allocation to the different monolignol pools is apparently determined by a combination of phenylalanine availability and cinnamate-4-hydroxylase/"p-coumarate-3-hydroxylase" (C4H/C3H) activities, as revealed by transcriptional and metabolic profiling. Downregulation of either phenylalanine ammonia lyase or cinnamate-4-hydroxylase thus predictably results in reduced lignin levels and impaired vascular integrity, as well as affecting related (phenylpropanoid-dependent) metabolism. Depletion of C3H activity also results in reduced lignin deposition, albeit with the latter being derived only from hydroxyphenyl (H) units, due to both the guaiacyl (G) and syringyl (S) pathways being blocked. Apparently the cells affected are unable to compensate for reduced G/S levels by increasing the amounts of H-components. The downstream metabolic networks for G-lignin enriched formation in both angiosperms and gymnosperms utilize specific cinnamoyl CoA O-methyltransferase (CCOMT), 4-coumarate:CoA ligase (4CL), cinnamoyl CoA reductase (CCR) and cinnamyl alcohol dehydrogenase (CAD) isoforms: however, these steps neither affect carbon allocation nor H/G designations, this being determined by C4H/C3H

Relational databases for rare disease study: application to vascular anomalies.

Science.gov (United States)

Perkins, Jonathan A; Coltrera, Marc D

2008-01-01

To design a relational database integrating clinical and basic science data needed for multidisciplinary treatment and research in the field of vascular anomalies. Based on data points agreed on by the American Society of Pediatric Otolaryngology (ASPO) Vascular Anomalies Task Force. The database design enables sharing of data subsets in a Health Insurance Portability and Accountability Act (HIPAA)-compliant manner for multisite collaborative trials. Vascular anomalies pose diagnostic and therapeutic challenges. Our understanding of these lesions and treatment improvement is limited by nonstandard terminology, severity assessment, and measures of treatment efficacy. The rarity of these lesions places a premium on coordinated studies among multiple participant sites. The relational database design is conceptually centered on subjects having 1 or more lesions. Each anomaly can be tracked individually along with their treatment outcomes. This design allows for differentiation between treatment responses and untreated lesions' natural course. The relational database design eliminates data entry redundancy and results in extremely flexible search and data export functionality. Vascular anomaly programs in the United States. A relational database correlating clinical findings and photographic, radiologic, histologic, and treatment data for vascular anomalies was created for stand-alone and multiuser networked systems. Proof of concept for independent site data gathering and HIPAA-compliant sharing of data subsets was demonstrated. The collaborative effort by the ASPO Vascular Anomalies Task Force to create the database helped define a common vascular anomaly data set. The resulting relational database software is a powerful tool to further the study of vascular anomalies and the development of evidence-based treatment innovation.

A Low-Complexity Subgroup Formation with QoS-Aware for Enhancing Multicast Services in LTE Networks

Science.gov (United States)

Algharem, M.; Omar, M. H.; Rahmat, R. F.; Budiarto, R.

2018-03-01

The high demand of Multimedia services on in Long Term Evolution (LTE) and beyond networks forces the networks operators to find a solution that can handle the huge traffic. Along with this, subgroup formation techniques are introduced to overcome the limitations of the Conventional Multicast Scheme (CMS) by splitting the multicast users into several subgroups based on the users’ channels quality signal. However, finding the best subgroup configuration with low complexity is need more investigations. In this paper, an efficient and simple subgroup formation mechanisms are proposed. The proposed mechanisms take the transmitter MAC queue in account. The effectiveness of the proposed mechanisms is evaluated and compared with CMS in terms of throughput, fairness, delay, Block Error Rate (BLER).

Low-dimensional models of ‘Neuro-glio-vascular unit’ for describing neural dynamics under normal and energy-starved conditions

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Karishma eChhabria

2016-03-01

Full Text Available The motivation of developing simple minimal models for neuro-glio-vascular system arises from a recent modeling study elucidating the bidirectional information flow within the neuro-glio-vascular system having 89 dynamic equations (Chander and Chakravarthy 2012. While this was one of the first attempts at formulating a comprehensive model for neuro-glia-vascular system, it poses severe restrictions in scaling up to network levels. On the contrary, low dimensional models are convenient devices in simulating large networks that also provide an intuitive understanding of the complex interactions occurring within the neuro-glio-vascular system. The key idea underlying the proposed models is to describe the glio-vascular system as a lumped system which takes neural firing rate as input and returns an ‘energy’ variable (analogous to ATP as output. To this end we present two models: Biophysical neuro-energy (Model #1 with 5 variables, comprising of KATP channel activity governed by neuronal ATP dynamics and the Dynamic threshold (Model #2 with 3 variables depicting the dependence of neural firing threshold on the ATP dynamics. Both the models show different firing regimes such as continuous spiking, phasic and tonic bursting depending on the ATP production coefficient, εp and external current. We then demonstrate that in a network comprising of such energy-dependent neuron units, εp could modulate the Local field potential (LFP frequency and amplitude. Interestingly, low frequency LFP dominates under low εp conditions, which is thought to be reminiscent of seizure-like activity observed in epilepsy. The proposed ‘neuron-energy’ unit may be implemented in building models of neuro-glio-vascular networks to simulate data obtained from multimodal neuroimaging systems such as fNIRS-EEG and fMRI-EEG. Such models could also provide a theoretical basis for devising optimal neurorehabilitation strategies such as non-invasive brain stimulation for

The effect of oil type on network formation by protein aggregates into oleogels

NARCIS (Netherlands)

Vries, de Auke; Lopez Gomez, Yuly; Linden, van der Erik; Scholten, Elke

2017-01-01

The aim of this study was to assess the effect of oil type on the network formation of heat-set protein aggregates in liquid oil. The gelling properties of such aggregates to structure oil into so-called ‘oleogels’ are related to both the particle-particle and particle-solvent interactions. To

Proangiogenic hematopoietic cells of monocytic origin: roles in vascular regeneration and pathogenic processes of systemic sclerosis.

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Yamaguchi, Yukie; Kuwana, Masataka

2013-02-01

New blood vessel formation is critical, not only for organ development and tissue regeneration, but also for various pathologic processes, such as tumor development and vasculopathy. The maintenance of the postnatal vascular system requires constant remodeling, which occurs through angiogenesis, vasculogenesis, and arteriogenesis. Vasculogenesis is mediated by the de novo differentiation of mature endothelial cells from endothelial progenitor cells (EPCs). Early studies provided evidence that bone marrow-derived CD14⁺ monocytes can serve as a subset of EPCs because of their expression of endothelial markers and ability to promote neovascularization in vitro and in vivo. However, the current consensus is that monocytic cells do not give rise to endothelial cells in vivo, but function as support cells, by promoting vascular formation and repair through their immediate recruitment to the site of vascular injury, secretion of proangiogenic factors, and differentiation into mural cells. These monocytes that function in a supporting role in vascular repair are now termed monocytic pro-angiogenic hematopoietic cells (PHCs). Systemic sclerosis (SSc) is a multisystem connective tissue disease characterized by excessive fibrosis and microvasculopathy, along with poor vascular formation and repair. We recently showed that in patients with SSc, circulating monocytic PHCs increase dramatically and have enhanced angiogenic potency. These effects may be induced in response to defective vascular repair machinery. Since CD14⁺ monocytes can also differentiate into fibroblast-like cells that produce extracellular matrix proteins, here we propose a new hypothesis that aberrant monocytic PHCs, once mobilized into circulation, may also contribute to the fibrotic process of SSc.

Deleterious effects of tributyltin on porcine vascular stem cells physiology.

Science.gov (United States)

Bernardini, Chiara; Zannoni, Augusta; Bertocchi, Martina; Bianchi, Francesca; Salaroli, Roberta; Botelho, Giuliana; Bacci, Maria Laura; Ventrella, Vittoria; Forni, Monica

2016-01-01

The vascular functional and structural integrity is essential for the maintenance of the whole organism and it has been demonstrated that different types of vascular progenitor cells resident in the vessel wall play an important role in this process. The purpose of the present research was to observe the effect of tributyltin (TBT), a risk factor for vascular disorders, on porcine Aortic Vascular Precursor Cells (pAVPCs) in term of cytotoxicity, gene expression profile, functionality and differentiation potential. We have demonstrated that pAVPCs morphology deeply changed following TBT treatment. After 48h a cytotoxic effect has been detected and Annexin binding assay demonstrated that TBT induced apoptosis. The transcriptional profile of characteristic pericyte markers has been altered: TBT 10nM substantially induced alpha-SMA, while, TBT 500nM determined a significant reduction of all pericyte markers. IL-6 protein detected in the medium of pAVPCs treated with TBT at both doses studied and with a dose response. TBT has interfered with normal pAVPC functionality preventing their ability to support a capillary-like network. In addition TBT has determined an increase of pAVPC adipogenic differentiation. In conclusion in the present paper we have demonstrated that TBT alters the vascular stem cells in terms of structure, functionality and differentiating capability, therefore effects of TBT in blood should be deeply explored to understand the potential vascular risk associated with the alteration of vascular stem cell physiology. Copyright © 2016 Elsevier Inc. All rights reserved.

The making of indigenous vascular prosthesis

Directory of Open Access Journals (Sweden)

Madathipat Unnikrishnan

2016-01-01

Full Text Available Background & objectives: Vascular illnesses are on the rise in India, due to increase in lifestyle diseases and demographic transition, requiring intervention to save life, organ or limbs using vascular prosthesis. The aim of this study was to develop indigenous large diameter vascular graft for treatment of patients with vascular pathologies. Methods: The South India Textile Research Association, at Coimbatore, Tamil Nadu, India, developed seamless woven polyester (Polyethylene terephthalate graft at its research wing. Further characterization and testing followed by clinical trials were conducted at Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India. Fifteen in vivo experiments were carried out in 1992-1994 in pigs as animal model. Controlled (phase I clinical trial in ten patients was performed along with control graft. Thereafter, phase II trial involved 22 patients who underwent multi-centre clinical trial in four centres across India. Results: Laboratory testing showed that polyester graft was non-toxic, non-leeching and non-haemolytic with preserved long-term quality, further confirming in pigs by implanting in thoracic aorta, comparable to control Dacron grafts. Perigraft incorporation and smooth neointima formation which are prime features of excellent healing characteristics, were noted at explantation at planned intervals. Subsequently in the phase I and II clinical trials, all patients had excellent recovery without mortality or device-related adverse events. Patients receiving the test graft were followed up for 10 and 5 years, respectively. Serial clinical, duplex scans and CT angiograms performed periodically confirmed excellent graft performance. Interpretation & conclusions: Indigenously developed Chitra vascular graft was comparable to commercially available Dacron graft, ready for clinical use at affordable cost to patients as against costly imported grafts.

Broncho-vascular fistulas from self-expanding metallic stents: A retrospective case review

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Chirag Choudhary

2013-01-01

Full Text Available To highlight a potentially fatal complication of broncho-vascular fistula arising from the self expanding metallic stent (SEMS placement. We retrospectively analyzed five patients with benign and malignant airway diseases, who developed tracheo/broncho-vascular fistulas following SEMS placement in our tertiary care setting. All patients received either Wallstent or Ultraflex® stent (Boston Scientific, Natick, MA between 1999 and 2007. All patients had received adjunct therapy such as balloon bronchoplasty, laser therapy or electrocautery. Most patients presented with massive hemoptysis. A total of 483 SEMS were placed during this period. SEMS placement can be complicated by Broncho-vascular fistula formation. True incidence and precise time interval between the insertion of stent and onset of this complication is unknown. Additional therapeutic modalities to maintain stent patency may enhance the risk of fistula formation. SEMS should only be used in a select sub-group of patients, after exhaustive evaluation of other treatment options. These cases provide evidence that broncho-vascular fistulas can develop at any time following SEMS placement, suggesting the need for a more cautious approach, especially while using them for a long term management. In benign airway disease, the stent should be removed as soon as healing has taken place.

Cellular Model of Atherogenesis Based on Pluripotent Vascular Wall Pericytes.

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Ivanova, Ekaterina A; Orekhov, Alexander N

2016-01-01

Pericytes are pluripotent cells that can be found in the vascular wall of both microvessels and large arteries and veins. They have distinct morphology with long branching processes and form numerous contacts with each other and with endothelial cells, organizing the vascular wall cells into a three-dimensional network. Accumulating evidence demonstrates that pericytes may play a key role in the pathogenesis of vascular disorders, including atherosclerosis. Macrovascular pericytes are able to accumulate lipids and contribute to growth and vascularization of the atherosclerotic plaque. Moreover, they participate in the local inflammatory process and thrombosis, which can lead to fatal consequences. At the same time, pericytes can represent a useful model for studying the atherosclerotic process and for the development of novel therapeutic approaches. In particular, they are suitable for testing various substances' potential for decreasing lipid accumulation induced by the incubation of cells with atherogenic low-density lipoprotein. In this review we will discuss the application of cellular models for studying atherosclerosis and provide several examples of successful application of these models to drug research.

Analyzing Structure and Function of Vascularization in Engineered Bone Tissue by Video-Rate Intravital Microscopy and 3D Image Processing.

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Pang, Yonggang; Tsigkou, Olga; Spencer, Joel A; Lin, Charles P; Neville, Craig; Grottkau, Brian

2015-10-01

Vascularization is a key challenge in tissue engineering. Three-dimensional structure and microcirculation are two fundamental parameters for evaluating vascularization. Microscopic techniques with cellular level resolution, fast continuous observation, and robust 3D postimage processing are essential for evaluation, but have not been applied previously because of technical difficulties. In this study, we report novel video-rate confocal microscopy and 3D postimage processing techniques to accomplish this goal. In an immune-deficient mouse model, vascularized bone tissue was successfully engineered using human bone marrow mesenchymal stem cells (hMSCs) and human umbilical vein endothelial cells (HUVECs) in a poly (D,L-lactide-co-glycolide) (PLGA) scaffold. Video-rate (30 FPS) intravital confocal microscopy was applied in vitro and in vivo to visualize the vascular structure in the engineered bone and the microcirculation of the blood cells. Postimage processing was applied to perform 3D image reconstruction, by analyzing microvascular networks and calculating blood cell viscosity. The 3D volume reconstructed images show that the hMSCs served as pericytes stabilizing the microvascular network formed by HUVECs. Using orthogonal imaging reconstruction and transparency adjustment, both the vessel structure and blood cells within the vessel lumen were visualized. Network length, network intersections, and intersection densities were successfully computed using our custom-developed software. Viscosity analysis of the blood cells provided functional evaluation of the microcirculation. These results show that by 8 weeks, the blood vessels in peripheral areas function quite similarly to the host vessels. However, the viscosity drops about fourfold where it is only 0.8 mm away from the host. In summary, we developed novel techniques combining intravital microscopy and 3D image processing to analyze the vascularization in engineered bone. These techniques have broad

Non-invasive vascular imaging: assessing tumour vascularity

International Nuclear Information System (INIS)

Delorme, S.; Knopp, M.V.

1998-01-01

Non-invasive assessment of vascularity is a new diagnostic approach to characterise tumours. Vascular assessment is based on the pathophysiology of tumour angiogenesis and its diagnostic implications for tumour biology, prognosis and therapy response. Two current techniques investigating vascular features in addition to morphology are Doppler ultrasonography and contrast-enhanced MRI. Diagnostic differentiation has been shown to be possible with Doppler, and a high degree of observed vascularity could be linked to an aggressive course of the disease. Dynamic MRI using gadolinium chelates is already used clinically to detect and differentiate tumours. The histological correlation shows that capillary permeability is increased in malignant tumours and is the best criterion for differentiation from benign processes. Permeability and perfusion factors seem to be more diagnostic than overall vessel density. New clinical applications are currently being established for therapy monitoring. Further instrumental developments will bring harmonic imaging in Doppler, and faster imaging techniques, higher spatial resolution and novel pharmacokinetic concepts in MRI. Upcoming contrast agents for both Doppler and MRI will further improve estimation of intratumoural blood volume and vascular permeability. (orig.)

Design Approaches to Myocardial and Vascular Tissue Engineering.

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Akintewe, Olukemi O; Roberts, Erin G; Rim, Nae-Gyune; Ferguson, Michael A H; Wong, Joyce Y

2017-06-21

Engineered tissues represent an increasingly promising therapeutic approach for correcting structural defects and promoting tissue regeneration in cardiovascular diseases. One of the challenges associated with this approach has been the necessity for the replacement tissue to promote sufficient vascularization to maintain functionality after implantation. This review highlights a number of promising prevascularization design approaches for introducing vasculature into engineered tissues. Although we focus on encouraging blood vessel formation within myocardial implants, we also discuss techniques developed for other tissues that could eventually become relevant to engineered cardiac tissues. Because the ultimate solution to engineered tissue vascularization will require collaboration between wide-ranging disciplines such as developmental biology, tissue engineering, and computational modeling, we explore contributions from each field.

Precise Localization and Formation Control of Swarm Robots via Wireless Sensor Networks

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Han Wu

2014-01-01

Full Text Available Precise localization and formation control are one of the key technologies to achieve coordination and control of swarm robots, which is also currently a bottleneck for practical applications of swarm robotic systems. Aiming at overcoming the limited individual perception and the difficulty of achieving precise localization and formation, a localization approach combining dead reckoning (DR with wireless sensor network- (WSN- based methods is proposed in this paper. Two kinds of WSN localization technologies are adopted in this paper, that is, ZigBee-based RSSI (received signal strength indication global localization and electronic tag floors for calibration of local positioning. First, the DR localization information is combined with the ZigBee-based RSSI position information using the Kalman filter method to achieve precise global localization and maintain the robot formation. Then the electronic tag floors provide the robots with their precise coordinates in some local areas and enable the robot swarm to calibrate its formation by reducing the accumulated position errors. Hence, the overall performance of localization and formation control of the swarm robotic system is improved. Both of the simulation results and the experimental results on a real schematic system are given to demonstrate the success of the proposed approach.

Direct 3D bioprinting of perfusable vascular constructs using a blend bioink.

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Jia, Weitao; Gungor-Ozkerim, P Selcan; Zhang, Yu Shrike; Yue, Kan; Zhu, Kai; Liu, Wanjun; Pi, Qingment; Byambaa, Batzaya; Dokmeci, Mehmet Remzi; Shin, Su Ryon; Khademhosseini, Ali

2016-11-01

Despite the significant technological advancement in tissue engineering, challenges still exist towards the development of complex and fully functional tissue constructs that mimic their natural counterparts. To address these challenges, bioprinting has emerged as an enabling technology to create highly organized three-dimensional (3D) vascular networks within engineered tissue constructs to promote the transport of oxygen, nutrients, and waste products, which can hardly be realized using conventional microfabrication techniques. Here, we report the development of a versatile 3D bioprinting strategy that employs biomimetic biomaterials and an advanced extrusion system to deposit perfusable vascular structures with highly ordered arrangements in a single-step process. In particular, a specially designed cell-responsive bioink consisting of gelatin methacryloyl (GelMA), sodium alginate, and 4-arm poly(ethylene glycol)-tetra-acrylate (PEGTA) was used in combination with a multilayered coaxial extrusion system to achieve direct 3D bioprinting. This blend bioink could be first ionically crosslinked by calcium ions followed by covalent photocrosslinking of GelMA and PEGTA to form stable constructs. The rheological properties of the bioink and the mechanical strengths of the resulting constructs were tuned by the introduction of PEGTA, which facilitated the precise deposition of complex multilayered 3D perfusable hollow tubes. This blend bioink also displayed favorable biological characteristics that supported the spreading and proliferation of encapsulated endothelial and stem cells in the bioprinted constructs, leading to the formation of biologically relevant, highly organized, perfusable vessels. These characteristics make this novel 3D bioprinting technique superior to conventional microfabrication or sacrificial templating approaches for fabrication of the perfusable vasculature. We envision that our advanced bioprinting technology and bioink formulation may also

In situ recording of particle network formation in liquids by ion conductivity measurements.

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Pfaffenhuber, Christian; Sörgel, Seniz; Weichert, Katja; Bele, Marjan; Mundinger, Tabea; Göbel, Marcus; Maier, Joachim

2011-09-21

The formation of fractal silica networks from a colloidal initial state was followed in situ by ion conductivity measurements. The underlying effect is a high interfacial lithium ion conductivity arising when silica particles are brought into contact with Li salt-containing liquid electrolytes. The experimental results were modeled using Monte Carlo simulations and tested using confocal fluorescence laser microscopy and ζ-potential measurements.

Performance evaluation of multilevel modulation formats using partial response for capacity upgrade in access network with limited electronic bandwidth

DEFF Research Database (Denmark)

Madsen, Peter; Suhr, Lau Frejstrup; Rodríguez Páez, Juan Sebastián

2016-01-01

We present a successful experimental evaluation of 4 level Pulse Amplitude Modulation (4-PAM) and Duobinary modulation. An experimental performance evaluation is presented for Duobinary 4 PAM and other modulation formats. All modulation formants used, may be considered to be implemented in future...... Passive Optical Network (PON) class access networks with limited electrical bandwidth. We compared NRZ, Duobinary, 4-PAM and Duobinary 4-PAM operating at 9 Gbaud over 20 km single mode fiber. The results provides an insight and guidelines on the utilization of these advanced modulation formats....

Formation of nano-hydroxyapatite crystal in situ in chitosan-pectin polyelectrolyte complex network

International Nuclear Information System (INIS)

Li Junjie; Zhu Dunwan; Yin Jianwei; Liu Yuxi; Yao Fanglian; Yao Kangde

2010-01-01

Hydroxyapatite (HA)/polysaccharide composites have been widely used in bone tissue engineering due to their chemical similarity to natural bone. Polymer matrix-mediated synthesis of nano-hydroxyapatite is one of the simplest models for biomimetic. In this article, the nano-hydroxyapatite/chitosan-pectin (nHCP) composites were prepared through in situ mineralization of hydroxyapatite in chitosan-pectin polyelectrolyte complex (PEC) network. The formation processes of nHCP were investigated by X-ray diffraction (XRD) analysis. The interactions between nHA crystal and chitosan-pectin PEC networks were studied using Fourier Transform Infrared Spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC). The morphology and structure of nHA crystal were characterized by XRD and Transmission Electron Microscope (TEM). Results suggested that the interfacial interactions between nano-hydroxyapatite crystal and chitosan-pectin PEC network assist the site specific nucleation and growth of nHA nanoparticles. The nHA crystals grow along the c-axis. In this process, pH value is the main factor to control the nucleation and growth of nHA crystal in chitosan-pectin PEC networks, because both the interactions' strength between nHA crystal and chitosan-pectin and diffusion rate of inorganic ions depend on the pH value of the reaction system. Apart from the pH value, the chitosan/pectin ratio and [Ca 2+ ] also take important effects on the formation of nHA crystal. An effective way to control the size of nHA crystal is to adjust the content of pectin and [Ca 2+ ]. It is interesting that the Zeta potential of nHCP composites is about - 30 mV when the chitosan/pectin ratio ≤ 1:1, and the dispersion solution of nHCP composites has higher stability, which provides the possibility to prepare 3D porous scaffolds with nHCP for bone tissue engineering.

Formation of nano-hydroxyapatite crystal in situ in chitosan-pectin polyelectrolyte complex network

Energy Technology Data Exchange (ETDEWEB)

Li Junjie [Department of Polymer Science and Key Laboratory of Systems Bioengineering of Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072 (China); Research Institute of Polymeric Materials, Tianjin University, Tianjin, 300072 (China); Zhu Dunwan [Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300072 (China); Yin Jianwei; Liu Yuxi [Department of Polymer Science and Key Laboratory of Systems Bioengineering of Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072 (China); Yao Fanglian, E-mail: yaofanglian@tju.edu.cn [Department of Polymer Science and Key Laboratory of Systems Bioengineering of Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072 (China); Yao Kangde [Research Institute of Polymeric Materials, Tianjin University, Tianjin, 300072 (China)

2010-07-20

Hydroxyapatite (HA)/polysaccharide composites have been widely used in bone tissue engineering due to their chemical similarity to natural bone. Polymer matrix-mediated synthesis of nano-hydroxyapatite is one of the simplest models for biomimetic. In this article, the nano-hydroxyapatite/chitosan-pectin (nHCP) composites were prepared through in situ mineralization of hydroxyapatite in chitosan-pectin polyelectrolyte complex (PEC) network. The formation processes of nHCP were investigated by X-ray diffraction (XRD) analysis. The interactions between nHA crystal and chitosan-pectin PEC networks were studied using Fourier Transform Infrared Spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC). The morphology and structure of nHA crystal were characterized by XRD and Transmission Electron Microscope (TEM). Results suggested that the interfacial interactions between nano-hydroxyapatite crystal and chitosan-pectin PEC network assist the site specific nucleation and growth of nHA nanoparticles. The nHA crystals grow along the c-axis. In this process, pH value is the main factor to control the nucleation and growth of nHA crystal in chitosan-pectin PEC networks, because both the interactions' strength between nHA crystal and chitosan-pectin and diffusion rate of inorganic ions depend on the pH value of the reaction system. Apart from the pH value, the chitosan/pectin ratio and [Ca{sup 2+}] also take important effects on the formation of nHA crystal. An effective way to control the size of nHA crystal is to adjust the content of pectin and [Ca{sup 2+}]. It is interesting that the Zeta potential of nHCP composites is about - 30 mV when the chitosan/pectin ratio {<=} 1:1, and the dispersion solution of nHCP composites has higher stability, which provides the possibility to prepare 3D porous scaffolds with nHCP for bone tissue engineering.

Rosuvastatin reduces neointima formation in a rat model of balloon injury

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Preusch MR

2010-11-01

Full Text Available Abstract Background Processes of restenosis, following arterial injury, are complex involving different cell types producing various cytokines and enzymes. Among those enzymes, smooth muscle cell-derived matrix metalloproteinases (MMPs are thought to take part in cell migration, degrading of extracellular matrix, and neointima formation. MMP-9, also known as gelatinase B, is expressed immediately after vascular injury and its expression and activity can be inhibited by statins. Using an established in vivo model of vascular injury, we investigated the effect of the HMG-CoA reductase inhibitor rosuvastatin on MMP-9 expression and neointima formation. Materials and methods 14-week old male Sprague Dawley rats underwent balloon injury of the common carotid artery. Half of the animals received rosuvastatin (20 mg/kg body weight/day via oral gavage, beginning 3 days prior to injury. Gelatinase activity and neointima formation were analyzed 3 days and 14 days after balloon injury, respectively. 14 days after vascular injury, proliferative activity was assessed by staining for Ki67. Results After 14 days, animals in the rosuvastatin group showed a decrease in total neointima formation (0.194 ± 0.01 mm2 versus 0.124 ± 0.02 mm2, p Conclusions Rosuvastatin attenuates neointima formation without affecting early MMP-9 activity in a rat model of vascular injury.

Platelet lysate gel and endothelial progenitors stimulate microvascular network formation in vitro: tissue engineering implications.

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Fortunato, Tiago M; Beltrami, Cristina; Emanueli, Costanza; De Bank, Paul A; Pula, Giordano

2016-05-04

Revascularisation is a key step for tissue regeneration and complete organ engineering. We describe the generation of human platelet lysate gel (hPLG), an extracellular matrix preparation from human platelets able to support the proliferation of endothelial colony forming cells (ECFCs) in 2D cultures and the formation of a complete microvascular network in vitro in 3D cultures. Existing extracellular matrix preparations require addition of high concentrations of recombinant growth factors and allow only limited formation of capillary-like structures. Additional advantages of our approach over existing extracellular matrices are the absence of any animal product in the composition hPLG and the possibility of obtaining hPLG from patients to generate homologous scaffolds for re-implantation. This discovery has the potential to accelerate the development of regenerative medicine applications based on implantation of microvascular networks expanded ex vivo or the generation of fully vascularised organs.

The hemostatic agent ethamsylate promotes platelet/leukocyte aggregate formation in a model of vascular injury.

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Hernandez, Maria Rosa; Alvarez-Guerra, Miriam; Escolar, Ginés; Chiavaroli, Carlo; Hannaert, Patrick; Garay, Ricardo P

2004-08-01

The hemostatic agent ethamsylate enhances membrane expression of P-selectin in human platelets, but whether this promotes platelet-leukocyte aggregate formation is unknown. Here we investigated this point by flow cytometry determination of human platelet-leukocyte aggregates under basal conditions and after whole-blood perfusion through a damaged rabbit aorta segment. Actions of ethamsylate on adhesive molecules of platelets and leukocytes were investigated in parallel. Under basal conditions, ethamsylate was unable to modify whole-blood platelet-leukocyte aggregation, but following whole-blood perfusion through a damaged vessel, ethamsylate produced a modest, but significant increase in platelet-leukocyte aggregates (48+/-21 and 45+/-26% above control levels at ethamsylate 20 and 40 microm respectively). In isolated leukocyte plasma membranes, 14C-ethamsylate specifically bound up to an amount of 660 pmol/mg protein. Moreover, at concentrations > or =1 microm, ethamsylate induced an important (100-200%) and significant increase in the P-selectin glycoprotein ligand 1 (PSGL-1) fluorescence signal in isolated leukocytes and was unable to significantly modify the percentage of CD11b-positive cells. However, no significant changes in aggregate formation were found when ethamsylate was incubated with isolated leukocytes and blood was reconstituted and perfused. In isolated platelet cell membranes, anti-P-selectin antibody and the anti-integrin RGD-containing pentapeptide (GRDGS) were unable to displace 14C-ethamsylate binding. In conclusion, ethamsylate specifically binds to plasma membranes of leukocytes, enhances membrane PSGL-1 expression and promotes leukocyte-platelet aggregation in whole-blood perfused through a damaged vascular segment. These results together with the previously observed enhancement of platelet P-selectin membrane expression [Thromb. Res. (2002)107:329-335] confirms and extends the view that ethamsylate acts on the first step of hemostasis, by

Aperiodic dynamics in a deterministic adaptive network model of attitude formation in social groups

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Ward, Jonathan A.; Grindrod, Peter

2014-07-01

Adaptive network models, in which node states and network topology coevolve, arise naturally in models of social dynamics that incorporate homophily and social influence. Homophily relates the similarity between pairs of nodes' states to their network coupling strength, whilst social influence causes coupled nodes' states to convergence. In this paper we propose a deterministic adaptive network model of attitude formation in social groups that includes these effects, and in which the attitudinal dynamics are represented by an activato-inhibitor process. We illustrate that consensus, corresponding to all nodes adopting the same attitudinal state and being fully connected, may destabilise via Turing instability, giving rise to aperiodic dynamics with sensitive dependence on initial conditions. These aperiodic dynamics correspond to the formation and dissolution of sub-groups that adopt contrasting attitudes. We discuss our findings in the context of cultural polarisation phenomena. Social influence. This reflects the fact that people tend to modify their behaviour and attitudes in response to the opinions of others [22-26]. We model social influence via diffusion: agents adjust their state according to a weighted sum (dictated by the evolving network) of the differences between their state and the states of their neighbours. Homophily. This relates the similarity of individuals' states to their frequency and strength of interaction [27]. Thus in our model, homophily drives the evolution of the weighted ‘social' network. A precise formulation of our model is given in Section 2. Social influence and homophily underpin models of social dynamics [21], which cover a wide range of sociological phenomena, including the diffusion of innovations [28-32], complex contagions [33-36], collective action [37-39], opinion dynamics [19,20,40,10,11,13,15,41,16], the emergence of social norms [42-44], group stability [45], social differentiation [46] and, of particular relevance

Self-Condensation Culture Enables Vascularization of Tissue Fragments for Efficient Therapeutic Transplantation

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Yoshinobu Takahashi

2018-05-01

Full Text Available Summary: Clinical transplantation of tissue fragments, including islets, faces a critical challenge because of a lack of effective strategies that ensure efficient engraftment through the timely integration of vascular networks. We recently developed a complex organoid engineering method by “self-condensation” culture based on mesenchymal cell-dependent contraction, thereby enabling dissociated heterotypic lineages including endothelial cells to self-organize in a spatiotemporal manner. Here, we report the successful adaptation of this method for generating complex tissues from diverse tissue fragments derived from various organs, including pancreatic islets. The self-condensation of human and mouse islets with endothelial cells not only promoted functionalization in culture but also massively improved post-transplant engraftment. Therapeutically, fulminant diabetic mice were more efficiently treated by a vascularized islet transplant compared with the conventional approach. Given the general limitations of post-transplant vascularization associated with 3D tissue-based therapy, our approach offers a promising means of enhancing efficacy in the context of therapeutic tissue transplantation. : Takahashi et al. report on generating vascularized islet tissue from humans and mice. After transplantation, vascularized islets significantly improve survival of diabetic mice, demonstrating the quick normalization of blood glucose compared with conventional islet transplantation. Keywords: tissue engineering, tissue-based therapy, vascularization, islet transplantation, organoid

Deep multi-scale location-aware 3D convolutional neural networks for automated detection of lacunes of presumed vascular origin.

Science.gov (United States)

Ghafoorian, Mohsen; Karssemeijer, Nico; Heskes, Tom; Bergkamp, Mayra; Wissink, Joost; Obels, Jiri; Keizer, Karlijn; de Leeuw, Frank-Erik; Ginneken, Bram van; Marchiori, Elena; Platel, Bram

2017-01-01

Lacunes of presumed vascular origin (lacunes) are associated with an increased risk of stroke, gait impairment, and dementia and are a primary imaging feature of the small vessel disease. Quantification of lacunes may be of great importance to elucidate the mechanisms behind neuro-degenerative disorders and is recommended as part of study standards for small vessel disease research. However, due to the different appearance of lacunes in various brain regions and the existence of other similar-looking structures, such as perivascular spaces, manual annotation is a difficult, elaborative and subjective task, which can potentially be greatly improved by reliable and consistent computer-aided detection (CAD) routines. In this paper, we propose an automated two-stage method using deep convolutional neural networks (CNN). We show that this method has good performance and can considerably benefit readers. We first use a fully convolutional neural network to detect initial candidates. In the second step, we employ a 3D CNN as a false positive reduction tool. As the location information is important to the analysis of candidate structures, we further equip the network with contextual information using multi-scale analysis and integration of explicit location features. We trained, validated and tested our networks on a large dataset of 1075 cases obtained from two different studies. Subsequently, we conducted an observer study with four trained observers and compared our method with them using a free-response operating characteristic analysis. Shown on a test set of 111 cases, the resulting CAD system exhibits performance similar to the trained human observers and achieves a sensitivity of 0.974 with 0.13 false positives per slice. A feasibility study also showed that a trained human observer would considerably benefit once aided by the CAD system.

Engineered, axially-vascularized osteogenic grafts from human adipose-derived cells to treat avascular necrosis of bone in a rat model.

Science.gov (United States)

Ismail, Tarek; Osinga, Rik; Todorov, Atanas; Haumer, Alexander; Tchang, Laurent A; Epple, Christian; Allafi, Nima; Menzi, Nadia; Largo, René D; Kaempfen, Alexandre; Martin, Ivan; Schaefer, Dirk J; Scherberich, Arnaud

2017-11-01

Avascular necrosis of bone (AVN) leads to sclerosis and collapse of bone and joints. The standard of care, vascularized bone grafts, is limited by donor site morbidity and restricted availability. The aim of this study was to generate and test engineered, axially vascularized SVF cells-based bone substitutes in a rat model of AVN. SVF cells were isolated from lipoaspirates and cultured onto porous hydroxyapatite scaffolds within a perfusion-based bioreactor system for 5days. The resulting constructs were inserted into devitalized bone cylinders mimicking AVN-affected bone. A ligated vascular bundle was inserted upon subcutaneous implantation of constructs in nude rats. After 1 and 8weeks in vivo, bone formation and vascularization were analyzed. Newly-formed bone was found in 80% of SVF-seeded scaffolds after 8weeks but not in unseeded controls. Human ALU+cells in the bone structures evidenced a direct contribution of SVF cells to bone formation. A higher density of regenerative, M2 macrophages was observed in SVF-seeded constructs. In both experimental groups, devitalized bone was revitalized by vascularized tissue after 8 weeks. SVF cells-based osteogenic constructs revitalized fully necrotic bone in a challenging AVN rat model of clinically-relevant size. SVF cells contributed to accelerated initial vascularization, to bone formation and to recruitment of pro-regenerative endogenous cells. Avascular necrosis (AVN) of bone often requires surgical treatment with autologous bone grafts, which is surgically demanding and restricted by significant donor site morbidity and limited availability. This paper describes a de novo engineered axially-vascularized bone graft substitute and tests the potential to revitalize dead bone and provide efficient new bone formation in a rat model. The engineering of an osteogenic/vasculogenic construct of clinically-relevant size with stromal vascular fraction of human adipose, combined to an arteriovenous bundle is described. This

Brain Vascular Malformation Consortium: Overview, Progress and Future Directions.

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Akers, Amy L; Ball, Karen L; Clancy, Marianne; Comi, Anne M; Faughnan, Marie E; Gopal-Srivastava, Rashmi; Jacobs, Thomas P; Kim, Helen; Krischer, Jeffrey; Marchuk, Douglas A; McCulloch, Charles E; Morrison, Leslie; Moses, Marsha; Moy, Claudia S; Pawlikowska, Ludmilla; Young, William L

2013-04-01

Brain vascular malformations are resource-intensive to manage effectively, are associated with serious neurological morbidity, lack specific medical therapies, and have no validated biomarkers for disease severity and progression. Investigators have tended to work in "research silos" with suboptimal cross-communication. We present here a paradigm for interdisciplinary collaboration to facilitate rare disease research. The Brain Vascular Malformation Consortium (BVMC) is a multidisciplinary, inter-institutional group of investigators, one of 17 consortia in the Office of Rare Disease Research Rare Disease Clinical Research Network (RDCRN). The diseases under study are: familial Cerebral Cavernous Malformations type 1, common Hispanic mutation (CCM1-CHM); Sturge-Weber Syndrome (SWS); and brain arteriovenous malformation in hereditary hemorrhagic telangiectasia (HHT). Each project is developing biomarkers for disease progression and severity, and has established scalable, relational databases for observational and longitudinal studies that are stored centrally by the RDCRN Data Management and Coordinating Center. Patient Support Organizations (PSOs) are a key RDCRN component in the recruitment and support of participants. The BVMC PSOs include Angioma Alliance, Sturge Weber Foundation , and HHT Foundation International . Our networks of clinical centers of excellence in SWS and HHT, as well as our PSOs, have enhanced BVMC patient recruitment. The BVMC provides unique and valuable resources to the clinical neurovascular community, and recently reported findings are reviewed. Future planned studies will apply successful approaches and insights across the three projects to leverage the combined resources of the BVMC and RDCRN in advancing new biomarkers and treatment strategies for patients with vascular malformations.

Network formation, governance, and evolution in public health: the North American Quitline Consortium case.

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Provan, Keith G; Beagles, Jonathan E; Leischow, Scott J

2011-01-01

Collaborative networks of health organizations have received a great deal of attention in recent years as a way of enhancing the flow of information and coordination of services. However, relatively little is known about how such networks are formed and evolve, especially outside a local, community-based setting. This article is an in-depth discussion of the evolution of the North American Quitline Consortium (NAQC). The NAQC is a network of U.S. and Canadian organizations that provide telephone-based counseling and related services to people trying to quit smoking. The research draws on data from interviews, documents, and a survey of NAQC members to assess how the network emerged, became formalized, and effectively governed. The findings provide an understanding of how multiregional public health networks evolve, while building on and extending the broader literature on organizational networks in other sectors and settings. Specifically, we found that the network form that ultimately emerged was a product of the back-and-forth interplay between the internal needs and goals of those organizations that would ultimately become network members, in this case, state-, and provincial-level tobacco quitline organizations. We also found that network formation, and then governance through a network administrative organization, was driven by important events and shifts in the external environment, including the impact and influence of major national organizations. The results of the study provide health care leaders and policy officials an understanding of how the activities of a large number of organizations having a common health goal, but spanning multiple states and countries, might be coordinated and integrated through the establishment of a formal network.

Age-related memory decline is associated with vascular and microglial degeneration in aged rats.

Science.gov (United States)

Zhang, Rong; Kadar, Tamar; Sirimanne, Ernest; MacGibbon, Alastair; Guan, Jian

2012-12-01

The hippocampus processes memory is an early target of aging-related biological and structural lesions, leading to memory decline. With absent neurodegeneration in the hippocampus, which identified in rodent model of normal aging the pathology underlying age-related memory impairment is not complete. The effective glial-vascular networks are the key for maintaining neuronal functions. The changes of glial cells and cerebral capillaries with age may contribute to memory decline. Thus we examined age associated changes in neurons, glial phenotypes and microvasculature in the hippocampus of aged rats with memory decline. Young adult (6 months) and aged (35 months) male rats (Fisher/Norway-Brown) were used. To evaluate memory, four days of acquisition phase of Morris water maze tasks were carried out in both age groups and followed by a probe trial 2 h after the acquisition. The brains were then collected for analysis using immunochemistry. The aged rats showed a delayed latency (pvascular and microglial degeneration with reduced vascular endothelial growth factor and elevated GFAP expression in the hippocampus. The data indicate the memory decline with age is associated with neuronal dysfunction, possibly due to impaired glial-vascular-neuronal networks, but not neuronal degeneration. Glial and vascular degeneration found in aged rats may represent early event of aging pathology prior to neuronal degeneration. Copyright © 2012 Elsevier B.V. All rights reserved.

Novel graphical approach as fouling pinch for increasing fouling formation period in heat exchanger network (HEN) state of the art

International Nuclear Information System (INIS)

Azad, Abazar Vahdat; Ghaebi, Hadi; Amidpour, Majid

2011-01-01

In this paper a new graphical tool is proposed for investigation of fouling formation period in heat exchanger networks (HEN). The objective of this paper is increasing the time that HEN can perform its desirable heat transfer operation without required cleaning process. In a typical heat exchanger network, fouling formation rate of some streams is more than other ones. The method obtained in this work is based on given more opportunity for fouling formation for streams with high fouling formation rate. In fact high fouling formation rate streams are replaced with low fouling formation rate streams between different heat exchangers so that more fouling formation opportunity may be given for HEN. Therefore the HEN cleaning time decreases in fixed time period and the high fouling formation streams should pass from the path that the low fouling formation rate stream previously has passed, and inversely. As a result, secondly stream with high fouling formation rate mixes with residues of primary stream (low fouling formation rate stream). Therefore we should consider to adoption and conformability of streams structures (for prevention of streams destruction) and thermal considerations (for desirable heat transfer). Outlet temperatures of hot and cold streams should state in predefined temperatures. For satisfying thermal consideration after streams replacement this approach can be used in plants that cleanliness and its operational costs are most important problem.

Differential Gene Expression of Primary Cultured Lymphatic and Blood Vascular Endothelial Cells

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Gregory M. Nelson

2007-12-01

Full Text Available Blood vascular endothelial cells (BECs and the developmentally related lymphatic endothelial cells (LECs create complementary, yet distinct vascular networks. Each endothelial cell type interacts with flowing fluid and circulating cells, yet each vascular system has evolved specialized gene expression programs and thus both cell types display different phenotypes. BECs and LECs express distinct genes that are unique to their specific vascular microenvironment. Tumors also take advantage of the molecules that are expressed in these vascular systems to enhance their metastatic potential. We completed transcriptome analyses on primary cultured LECs and BECs, where each comparative set was isolated from the same individual. Differences were resolved in the expression of several major categories, such as cell adhesion molecules (CAMs, cytokines, cytokine receptors. We have identified new molecules that are associated with BECs (e.g., claudin-9, CXCL11, neurexin-1, neurexin-2, the neuronal growth factor regulator-1 and LECs (e.g., claudin-7, CD58, hyaluronan and proteoglycan link protein 1 (HAPLN1, the poliovirus receptor-related 3 molecule that may lead to novel therapeutic treatments for diseases of lymphatic or blood vessels, including metastasis of cancer to lymph nodes or distant organs.

Optical Coherence Tomography Angiography in Retinal Vascular Diseases and Choroidal Neovascularization

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Rodolfo Mastropasqua

2015-01-01

Full Text Available Purpose. To assess the ability of optical coherence tomography-angiography (OCT-A to show and analyze retinal vascular patterns and the choroidal neovascularization (CNV in retinal vascular diseases. Methods. Seven eyes of seven consecutive patients with retinal vascular diseases were examined. Two healthy subjects served as controls. All eyes were scanned with the SD-OCT XR Avanti (Optovue Inc, Fremont CA, USA. Split spectrum amplitude decorrelation angiography algorithm was used to identify the blood flow within the tissue. Fluorescein angiography (FA and indocyanine green angiography (ICGA with Spectralis HRA + OCT (Heidelberg Engineering GmbH were performed. Results. In healthy subjects OCT-A visualized major macular vessels and detailed capillary networks around the foveal avascular zone. Patients were affected with myopic CNV (2 eyes, age-related macular degeneration related (2, branch retinal vein occlusion (BRVO (2, and branch retinal artery occlusion (BRAO (1. OCT-A images provided distinct vascular patterns, distinguishing perfused and nonperfused areas in BRVO and BRAO and recognizing the presence, location, and size of CNV. Conclusions. OCT-A provides detailed images of retinal vascular plexuses and quantitative data of pathologic structures. Further studies are warranted to define the role of OCT-A in the assessment of retinovascular diseases, with respect to conventional FA and ICG-A.

Becoming popular: interpersonal emotion regulation predicts relationship formation in real life social networks

Science.gov (United States)

Niven, Karen; Garcia, David; van der Löwe, Ilmo; Holman, David; Mansell, Warren

2015-01-01

Building relationships is crucial for satisfaction and success, especially when entering new social contexts. In the present paper, we investigate whether attempting to improve others’ feelings helps people to make connections in new networks. In Study 1, a social network study following new networks of people for a 12-week period indicated that use of interpersonal emotion regulation (IER) strategies predicted growth in popularity, as indicated by other network members’ reports of spending time with the person, in work and non-work interactions. In Study 2, linguistic analysis of the tweets from over 8000 Twitter users from formation of their accounts revealed that use of IER predicted greater popularity in terms of the number of followers gained. However, not all types of IER had positive effects. Behavioral IER strategies (which use behavior to reassure or comfort in order to regulate affect) were associated with greater popularity, while cognitive strategies (which change a person’s thoughts about his or her situation or feelings in order to regulate affect) were negatively associated with popularity. Our findings have implications for our understanding of how new relationships are formed, highlighting the important the role played by intentional emotion regulatory processes. PMID:26483718

Becoming popular: Interpersonal emotion regulation predicts relationship formation in real life social networks

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Karen eNiven

2015-09-01

Full Text Available Building relationships is crucial for satisfaction and success, especially when entering new social contexts. In the present paper, we investigate whether attempting to improve others’ feelings helps people to make connections in new networks. In Study 1, a social network study following new networks of people for a twelve-week period indicated that use of interpersonal emotion regulation (IER strategies predicted growth in popularity, as indicated by other network members’ reports of spending time with the person, in work and non-work interactions. In Study 2, linguistic analysis of the tweets from over 8000 Twitter users from formation of their accounts revealed that use of IER predicted greater popularity in terms of the number of followers gained. However, not all types of IER had positive effects. Behavioral IER strategies (which use behavior to reassure or comfort in order to regulate affect were associated with greater popularity, while cognitive strategies (which change a person’s thoughts about his or her situation or feelings in order to regulate affect were negatively associated with popularity. Our findings have implications for our understanding of how new relationships are formed, highlighting the important the role played by intentional emotion regulatory processes.

Bosutinib, dasatinib, imatinib, nilotinib, and ponatinib differentially affect the vascular molecular pathways and functionality of human endothelial cells.

Science.gov (United States)

Gover-Proaktor, Ayala; Granot, Galit; Pasmanik-Chor, Metsada; Pasvolsky, Oren; Shapira, Saar; Raz, Oshrat; Raanani, Pia; Leader, Avi

2018-05-09

The tyrosine kinase inhibitors (TKIs), nilotinib, ponatinib, and dasatinib (but not bosutinib or imatinib), are associated with vascular adverse events (VAEs) in chronic myeloid leukemia (CML). Though the mechanism is inadequately understood, an effect on vascular cells has been suggested. We investigated the effect of imatinib, nilotinib, dasatinib, bosutinib, and ponatinib on tube formation, cell viability, and gene expression of human vascular endothelial cells (HUVECs). We found a distinct genetic profile in HUVECs treated with dasatinib, ponatinib, and nilotinib compared to bosutinib and imatinib, who resembled untreated samples. However, unique gene expression and molecular pathway alterations were detected between dasatinib, ponatinib, and nilotinib. Angiogenesis/blood vessel-related pathways and HUVEC function (tube formation/viability) were adversely affected by dasatinib, ponatinib, and nilotinib but not by imatinib or bosutinib. These results correspond to the differences in VAE profiles of these TKIs, support a direct effect on vascular cells, and provide direction for future research.

Computer-aided design of microvasculature systems for use in vascular scaffold production

International Nuclear Information System (INIS)

Mondy, William Lafayette; Cameron, Don; Timmermans, Jean-Pierre; De Clerck, Nora; Sasov, Alexander; Casteleyn, Christophe; Piegl, Les A

2009-01-01

In vitro biomedical engineering of intact, functional vascular networks, which include capillary structures, is a prerequisite for adequate vascular scaffold production. Capillary structures are necessary since they provide the elements and compounds for the growth, function and maintenance of 3D tissue structures. Computer-aided modeling of stereolithographic (STL) micro-computer tomographic (micro-CT) 3D models is a technique that enables us to mimic the design of vascular tree systems containing capillary beds, found in tissues. In our first paper (Mondy et al 2009 Tissue Eng. at press), using micro-CT, we studied the possibility of using vascular tissues to produce data capable of aiding the design of vascular tree scaffolding, which would help in the reverse engineering of a complete vascular tree system including capillary bed structures. In this paper, we used STL models of large datasets of computer-aided design (CAD) data of vascular structures which contained capillary structures that mimic those in the dermal layers of rabbit skin. Using CAD software we created from 3D STL models a bio-CAD design for the development of capillary-containing vascular tree scaffolding for skin. This method is designed to enhance a variety of therapeutic protocols including, but not limited to, organ and tissue repair, systemic disease mediation and cell/tissue transplantation therapy. Our successful approach to in vitro vasculogenesis will allow the bioengineering of various other types of 3D tissue structures, and as such greatly expands the potential applications of biomedical engineering technology into the fields of biomedical research and medicine.

Computer-aided design of microvasculature systems for use in vascular scaffold production

Energy Technology Data Exchange (ETDEWEB)

Mondy, William Lafayette [Department of Chemical and Biomedical Engineering, University of South Florida, FL (United States); Cameron, Don [Department of Pathology and Cell Biology, College of Medicine, University of South Florida, FL (United States); Timmermans, Jean-Pierre [Department of Veterinary Sciences, University of Antwerp (Belgium); De Clerck, Nora [Department of Biomedical Sciences University of Antwerp (Belgium); Sasov, Alexander [Skyscan (Belgium); Casteleyn, Christophe [College of Veterinary Medicine, Ghent University (Belgium); Piegl, Les A [Department of Computer Science and Engineering, University of South Florida, FL (United States)

2009-09-15

In vitro biomedical engineering of intact, functional vascular networks, which include capillary structures, is a prerequisite for adequate vascular scaffold production. Capillary structures are necessary since they provide the elements and compounds for the growth, function and maintenance of 3D tissue structures. Computer-aided modeling of stereolithographic (STL) micro-computer tomographic (micro-CT) 3D models is a technique that enables us to mimic the design of vascular tree systems containing capillary beds, found in tissues. In our first paper (Mondy et al 2009 Tissue Eng. at press), using micro-CT, we studied the possibility of using vascular tissues to produce data capable of aiding the design of vascular tree scaffolding, which would help in the reverse engineering of a complete vascular tree system including capillary bed structures. In this paper, we used STL models of large datasets of computer-aided design (CAD) data of vascular structures which contained capillary structures that mimic those in the dermal layers of rabbit skin. Using CAD software we created from 3D STL models a bio-CAD design for the development of capillary-containing vascular tree scaffolding for skin. This method is designed to enhance a variety of therapeutic protocols including, but not limited to, organ and tissue repair, systemic disease mediation and cell/tissue transplantation therapy. Our successful approach to in vitro vasculogenesis will allow the bioengineering of various other types of 3D tissue structures, and as such greatly expands the potential applications of biomedical engineering technology into the fields of biomedical research and medicine.

Computer-aided design of microvasculature systems for use in vascular scaffold production.

Science.gov (United States)

Mondy, William Lafayette; Cameron, Don; Timmermans, Jean-Pierre; De Clerck, Nora; Sasov, Alexander; Casteleyn, Christophe; Piegl, Les A

2009-09-01

In vitro biomedical engineering of intact, functional vascular networks, which include capillary structures, is a prerequisite for adequate vascular scaffold production. Capillary structures are necessary since they provide the elements and compounds for the growth, function and maintenance of 3D tissue structures. Computer-aided modeling of stereolithographic (STL) micro-computer tomographic (micro-CT) 3D models is a technique that enables us to mimic the design of vascular tree systems containing capillary beds, found in tissues. In our first paper (Mondy et al 2009 Tissue Eng. at press), using micro-CT, we studied the possibility of using vascular tissues to produce data capable of aiding the design of vascular tree scaffolding, which would help in the reverse engineering of a complete vascular tree system including capillary bed structures. In this paper, we used STL models of large datasets of computer-aided design (CAD) data of vascular structures which contained capillary structures that mimic those in the dermal layers of rabbit skin. Using CAD software we created from 3D STL models a bio-CAD design for the development of capillary-containing vascular tree scaffolding for skin. This method is designed to enhance a variety of therapeutic protocols including, but not limited to, organ and tissue repair, systemic disease mediation and cell/tissue transplantation therapy. Our successful approach to in vitro vasculogenesis will allow the bioengineering of various other types of 3D tissue structures, and as such greatly expands the potential applications of biomedical engineering technology into the fields of biomedical research and medicine.

Nitric oxide is a key molecule in migraine and other vascular headaches

DEFF Research Database (Denmark)

Olesen, J; Thomsen, L L; Iversen, Helle Klingenberg

1994-01-01

Nitric oxide (NO) may play a key role in migraine and other vascular headaches since glyceryl trinitrate (a donor of NO) and histamine (which probably activates endothelial NO formation) both cause a pulsating dose-dependent headache with several migrainous characteristics. At relatively high doses...... Olesen, Lars Thomsen and Helle Iversen suggest that migraine may be caused by increased amounts and/or affinity of an enzyme in the NO-triggered cascade of reactions. NO may also be involved in the pathogenesis of other vascular headaches....

NASAs VESGEN: Systems Analysis of Vascular Phenotypes from Stress and Other Signaling Pathways Using GeneLab.

Science.gov (United States)

Parsons-Wingerter, Patricia A.; Weitzel, Alexander; Vyas, Ruchi J.; Murray, Matthew C.; Wyatt, Sarah E.

2016-01-01

One fundamental requirement shared by humans with all higher terrestrial life forms, including insect wings, higher land plants and other vertebrates, is a complex, fractally branching vascular system. NASA's VESsel GENeration Analysis (VESGEN) software maps and quantifies vascular trees, networks, and tree-network composites according to weighted physiological rules such as vessel connectivity, tapering and bifurcational branching. According to fluid dynamics, successful vascular transport requires a complex distributed system of highly regulated laminar flow. Microvascular branching rules within vertebrates, dicot leaves and the other organisms therefore display many similarities. One unifying perspective is that vascular patterning offers a useful readout that necessarily integrates complex molecular signaling pathways. VESGEN has elucidated changes in vascular pattern resulting from inflammatory, stress response, developmental and other signaling within numerous tissues and major model organisms studied for Space Biology. For a new VESGEN systems approach, we analyzed differential gene expression in leaves of Arabidopsis thaliana reported by GeneLab (GLDS-7) for spaceflight. Vascular-related changes in leaf gene expression were identified that can potentially be phenocopied by mutants in ground-based experiments. To link transcriptional, protein and other molecular change with phenotype, alterations in the Euclidean and dynamic dimensions (x,y,t) of vascular patterns for Arabidopsis leaves and other model species are being co-localized with signaling patterns of single molecular expression analyzed as information dimensions (i,j,k,...). Previously, Drosophila microarray data returned from space suggested significant changes in genes related to wing venation development that include EGF, Notch, Hedghog, Wingless and Dpp signaling. Phenotypes of increasingly abnormal ectopic wing venation in the (non-spaceflight) Drosophila wing generated by overexpression of a

A Novel Strategy to Engineer Pre-Vascularized Full-Length Dental Pulp-like Tissue Constructs.

Science.gov (United States)

Athirasala, Avathamsa; Lins, Fernanda; Tahayeri, Anthony; Hinds, Monica; Smith, Anthony J; Sedgley, Christine; Ferracane, Jack; Bertassoni, Luiz E

2017-06-12

The requirement for immediate vascularization of engineered dental pulp poses a major hurdle towards successful implementation of pulp regeneration as an effective therapeutic strategy for root canal therapy, especially in adult teeth. Here, we demonstrate a novel strategy to engineer pre-vascularized, cell-laden hydrogel pulp-like tissue constructs in full-length root canals for dental pulp regeneration. We utilized gelatin methacryloyl (GelMA) hydrogels with tunable physical and mechanical properties to determine the microenvironmental conditions (microstructure, degradation, swelling and elastic modulus) that enhanced viability, spreading and proliferation of encapsulated odontoblast-like cells (OD21), and the formation of endothelial monolayers by endothelial colony forming cells (ECFCs). GelMA hydrogels with higher polymer concentration (15% w/v) and stiffness enhanced OD21 cell viability, spreading and proliferation, as well as endothelial cell spreading and monolayer formation. We then fabricated pre-vascularized, full-length, dental pulp-like tissue constructs by dispensing OD21 cell-laden GelMA hydrogel prepolymer in root canals of extracted teeth and fabricating 500 µm channels throughout the root canals. ECFCs seeded into the microchannels successfully formed monolayers and underwent angiogenic sprouting within 7 days in culture. In summary, the proposed approach is a simple and effective strategy for engineering of pre-vascularized dental pulp constructs offering potentially beneficial translational outcomes.

NETWORK FOLKLORE AND ITS ROLE IN THE FORMATION OF A COLLECTIVE COGNITIVE SPACE

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Anastasija Belovodskaja

2014-04-01

Full Text Available The global implementation of information-communicative technologies into every sphere of human activity is being accompanied by the emergence of new forms of communication, le­ading to inevitable changes in the means of both the representation and reception of information. In this respect, the field of interest encompasses research into modern anonymous network creative writing, which, as a result of the technological qualities of the Internet space, produces such texts that require particular skills in both comprehension and reproduction. In turn, the products of network folklore, as they spontaneously spread on the Internet, acquire the status of particular signs of a precedent nature. At the same time, the very nature of anonymous network creative writing—amusing and colloquial—raises the attractiveness of such texts and facilitates their reception, allowing them to be used for manipulative aims. The fact that such network folklore can influence the process of idea-formation in society is predetermined by the fact that, by definition, it is the milieu where collective representations are condensed and transmitted. Thus, network folklore is in the focus of attention not only in folklore studies, but is extremely topical for research in such fields as cognitive science, linguistic-cultural studies, public relations, speech effect, and any others which take interest in the processes of keeping, receiving, and transmitting information.

Axon guidance molecules in vascular patterning.

Science.gov (United States)

Adams, Ralf H; Eichmann, Anne

2010-05-01

Endothelial cells (ECs) form extensive, highly branched and hierarchically organized tubular networks in vertebrates to ensure the proper distribution of molecular and cellular cargo in the vertebrate body. The growth of this vascular system during development, tissue repair or in disease conditions involves the sprouting, migration and proliferation of endothelial cells in a process termed angiogenesis. Surprisingly, specialized ECs, so-called tip cells, which lead and guide endothelial sprouts, share many feature with another guidance structure, the axonal growth cone. Tip cells are motile, invasive and extend numerous filopodial protrusions sensing growth factors, extracellular matrix and other attractive or repulsive cues in their tissue environment. Axonal growth cones and endothelial tip cells also respond to signals belonging to the same molecular families, such as Slits and Roundabouts, Netrins and UNC5 receptors, Semaphorins, Plexins and Neuropilins, and Eph receptors and ephrin ligands. Here we summarize fundamental principles of angiogenic growth, the selection and function of tip cells and the underlying regulation by guidance cues, the Notch pathway and vascular endothelial growth factor signaling.

Meteorological Support Interface Control Working Group (MSICWG) Instrumentation, Data Format, and Networks Document

Science.gov (United States)

Brenton, James; Roberts, Barry C.

2017-01-01

The purpose of this document is to provide an overview of instrumentation discussed at the Meteorological Interface Control Working Group (MSICWG), a reference for data formats currently used by members of the group, a summary of proposed formats for future use by the group, an overview of the data networks of the group's members. This document will be updated as new systems are introduced, old systems are retired, and when the MSICWG community necessitates a change to the formats. The MSICWG consists of personnel from the National Aeronautics and Space Administration (NASA) Kennedy Space Center (KSC), NASA Marshall Space Flight Center (MSFC), NASA Johnson Space Center (JSC), National Oceanic and Atmospheric Administration National Weather Service Spaceflight Meteorology Group (SMG), and the United States Air Force (USAF) 45th Space Wing and Weather Squadron. The purpose of the group is to coordinate the distribution of weather related data to support NASA space launch related activities.

Vascular niche promotes hematopoietic multipotent progenitor formation from pluripotent stem cells

Science.gov (United States)

Gori, Jennifer L.; Butler, Jason M.; Chan, Yan-Yi; Chandrasekaran, Devikha; Poulos, Michael G.; Ginsberg, Michael; Nolan, Daniel J.; Elemento, Olivier; Wood, Brent L.; Adair, Jennifer E.; Rafii, Shahin; Kiem, Hans-Peter

2015-01-01

Pluripotent stem cells (PSCs) represent an alternative hematopoietic stem cell (HSC) source for treating hematopoietic disease. The limited engraftment of human PSC–derived (hPSC-derived) multipotent progenitor cells (MPP) has hampered the clinical application of these cells and suggests that MPP require additional cues for definitive hematopoiesis. We hypothesized that the presence of a vascular niche that produces Notch ligands jagged-1 (JAG1) and delta-like ligand-4 (DLL4) drives definitive hematopoiesis. We differentiated hes2 human embryonic stem cells (hESC) and Macaca nemestrina–induced PSC (iPSC) line-7 with cytokines in the presence or absence of endothelial cells (ECs) that express JAG1 and DLL4. Cells cocultured with ECs generated substantially more CD34+CD45+ hematopoietic progenitors compared with cells cocultured without ECs or with ECs lacking JAG1 or DLL4. EC-induced cells exhibited Notch activation and expressed HSC-specific Notch targets RUNX1 and GATA2. EC-induced PSC-MPP engrafted at a markedly higher level in NOD/SCID/IL-2 receptor γ chain–null (NSG) mice compared with cytokine-induced cells, and low-dose chemotherapy-based selection further increased engraftment. Long-term engraftment and the myeloid-to-lymphoid ratio achieved with vascular niche induction were similar to levels achieved for cord blood–derived MPP and up to 20-fold higher than those achieved with hPSC-derived MPP engraftment. Our findings indicate that endothelial Notch ligands promote PSC-definitive hematopoiesis and production of long-term engrafting CD34+ cells, suggesting these ligands are critical for HSC emergence. PMID:25664855

Wnt5a Regulates the Assembly of Human Adipose Derived Stromal Vascular Fraction-Derived Microvasculatures.

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Venkat M Ramakrishnan

Full Text Available Human adipose-derived stromal vascular fraction (hSVF cells are an easily accessible, heterogeneous cell system that can spontaneously self-assemble into functional microvasculatures in vivo. However, the mechanisms underlying vascular self-assembly and maturation are poorly understood, therefore we utilized an in vitro model to identify potential in vivo regulatory mechanisms. We utilized passage one (P1 hSVF because of the rapid UEA1+ endothelium (EC loss at even P2 culture. We exposed hSVF cells to a battery of angiogenesis inhibitors and found that the pan-Wnt inhibitor IWP2 produced the most significant hSVF-EC networking decrease (~25%. To determine which Wnt isoform(s and receptor(s may be involved, hSVF was screened by PCR for isoforms associated with angiogenesis, with only WNT5A and its receptor, FZD4, being expressed for all time points observed. Immunocytochemistry confirmed Wnt5a protein expression by hSVF. To see if Wnt5a alone could restore IWP2-induced EC network inhibition, recombinant human Wnt5a (0-150 ng/ml was added to IWP2-treated cultures. The addition of rhWnt5a significantly increased EC network area and significantly decreased the ratio of total EC network length to EC network area compared to untreated controls. To determine if Wnt5a mediates in vivo microvascular self-assembly, 3D hSVF constructs containing an IgG isotype control, anti-Wnt5a neutralizing antibody or rhWnt5a were implanted subcutaneously for 2w in immune compromised mice. Compared to IgG controls, anti-Wnt5a treatment significantly reduced vessel length density by ~41%, while rhWnt5a significantly increased vessel length density by ~62%. However, anti-Wnt5a or rhWnt5a did not significantly affect the density of segments and nodes, both of which measure vascular complexity. Taken together, this data demonstrates that endogenous Wnt5a produced by hSVF plays a regulatory role in microvascular self-assembly in vivo. These findings also suggest that

Industrie 4.0: Network Formation on a Distributed Manufacturing Project

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Luiz Fernando Cardoso dos Santos Durão

2017-09-01

Full Text Available The integration of modern internet technology and manufacturing technology, which has been denominated Industrie 4.0, allows for distributed manufacturing using additive manufacturing on a global scale with the integration of machines and processes. However, distributed manufacturing poses many challenges for standardization, quality control and management of information in different manufacturing sites. This article aims to investigate the formation of networks in distributed manufacturing projects, identifying the stake-holders and types of connections throughout the project. The methodological approach used was longitudinal action research for a distributed manufacturing project with a focus on flexible manufacturing. The central plant was located in Germany and the supplier located in Brazil, with a partnership between the Polytechnic School of the University of São Paulo and the Technical University of Darmstadt, Germany. The design and engineering that spawned the product model was developed in Germany, while the additive manufacturing site, the structure, and machinery was developed in Brazil, forming a development and distributed manufacturing network. The results showed how organized the communication and knowledge sharing was among those involved in the distributed manufacturing project, as well as an understanding of what kind of knowledge is shared among those involved.

Social factors shaping the formation of a multi-stakeholder trails network group for the Monongahela National Forest, West Virginia

Science.gov (United States)

Karen Robinson; Steven Selin; Chad Pierskalla

2009-01-01

This paper reports the results and management implications of a longitudinal research study examining the social factors affecting the formation of a trails network advisory group for the Monongahela National Forest (MNF) in West Virginia. A collaborative process of creating an MNF trails network with input from local users and stakeholders has been largely...

Remodeling the Vascular Microenvironment of Glioblastoma with α-Particles.

Science.gov (United States)

Behling, Katja; Maguire, William F; Di Gialleonardo, Valentina; Heeb, Lukas E M; Hassan, Iman F; Veach, Darren R; Keshari, Kayvan R; Gutin, Philip H; Scheinberg, David A; McDevitt, Michael R

2016-11-01

Tumors escape antiangiogenic therapy by activation of proangiogenic signaling pathways. Bevacizumab is approved for the treatment of recurrent glioblastoma, but patients inevitably develop resistance to this angiogenic inhibitor. We previously investigated targeted α-particle therapy with 225 Ac-E4G10 as an antivascular approach and showed increased survival and tumor control in a high-grade transgenic orthotopic glioblastoma model. Here, we investigated changes in tumor vascular morphology and functionality caused by 225 Ac-E4G10. We investigated remodeling of the tumor microenvironment in transgenic Ntva glioblastoma mice using a therapeutic 7.4-kBq dose of 225 Ac-E4G10. Immunofluorescence and immunohistochemical analyses imaged morphologic changes in the tumor blood-brain barrier microenvironment. Multicolor flow cytometry quantified the endothelial progenitor cell population in the bone marrow. Diffusion-weighted MR imaged functional changes in the tumor vascular network. The mechanism of drug action is a combination of remodeling of the glioblastoma vascular microenvironment, relief of edema, and depletion of regulatory T and endothelial progenitor cells. The primary remodeling event is the reduction of both endothelial and perivascular cell populations. Tumor-associated edema and necrosis were lessened, resulting in increased perfusion and reduced diffusion. Pharmacologic uptake of dasatinib into tumor was enhanced after α-particle therapy. Targeted antivascular α-particle radiation remodels the glioblastoma vascular microenvironment via a multimodal mechanism of action and provides insight into the vascular architecture of platelet-derived growth factor-driven glioblastoma. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Modelling the development and arrangement of the primary vascular structure in plants.

Science.gov (United States)

Cartenì, Fabrizio; Giannino, Francesco; Schweingruber, Fritz Hans; Mazzoleni, Stefano

2014-09-01

The process of vascular development in plants results in the formation of a specific array of bundles that run throughout the plant in a characteristic spatial arrangement. Although much is known about the genes involved in the specification of procambium, phloem and xylem, the dynamic processes and interactions that define the development of the radial arrangement of such tissues remain elusive. This study presents a spatially explicit reaction-diffusion model defining a set of logical and functional rules to simulate the differentiation of procambium, phloem and xylem and their spatial patterns, starting from a homogeneous group of undifferentiated cells. Simulation results showed that the model is capable of reproducing most vascular patterns observed in plants, from primitive and simple structures made up of a single strand of vascular bundles (protostele), to more complex and evolved structures, with separated vascular bundles arranged in an ordered pattern within the plant section (e.g. eustele). The results presented demonstrate, as a proof of concept, that a common genetic-molecular machinery can be the basis of different spatial patterns of plant vascular development. Moreover, the model has the potential to become a useful tool to test different hypotheses of genetic and molecular interactions involved in the specification of vascular tissues.

Role of the Vasa Vasorum and Vascular Resident Stem Cells in Atherosclerosis

Directory of Open Access Journals (Sweden)

Jun-ichi Kawabe

2014-01-01

Full Text Available Atherosclerosis is considered an “inside-out” response, that begins with the dysfunction of intimal endothelial cells and leads to neointimal plaque formation. The adventitia of large blood vessels has been recognized as an active part of the vessel wall that is involved in the process of atherosclerosis. There are characteristic changes in the adventitial vasa vasorum that are associated with the development of atheromatous plaques. However, whether vasa vasorum plays a causative or merely reactive role in the atherosclerotic process is not completely clear. Recent studies report that the vascular wall contains a number of stem/progenitor cells that may contribute to vascular remodeling. Microvessels serve as the vascular niche that maintains the resident stem/progenitor cells of the tissue. Therefore, the vasa vasorum may contribute to vascular remodeling through not only its conventional function as a blood conducting tube, but also its new conceptual function as a stem cell reservoir. This brief review highlights the recent advances contributing to our understanding of the role of the adventitial vasa vasorum in the atherosclerosis and discusses new concept that involves vascular-resident factors, the vasa vasorum and its associated vascular-resident stem cells, in the atherosclerotic process.

Evidence that tumor necrosis factor-related apoptosis inducing ligand (TRAIL) inhibits angiogenesis by inducing vascular endothelial cell apoptosis

International Nuclear Information System (INIS)

Chen, Pei-Lin; Easton, Alexander S.

2010-01-01

Tumor necrosis factor (TNF) and its related ligands TNF-related apoptosis inducing ligand (TRAIL) and Fas ligand (FasL) play roles in the regulation of vascular responses, but their effect on the formation of new blood vessels (angiogenesis) is unclear. Therefore, we have examined the effects of these ligands on angiogenesis modeled with primary cultures of human umbilical vein endothelial cells (HUVEC). To examine angiogenesis in the context of the central nervous system, we have also modeled cerebral angiogenesis with the human brain endothelial cell line hCMEC/D3. Parameters studied were bromodeoxyuridine (BrdU) incorporation and cell number (MTT) assay (to assess endothelial proliferation), scratch assay (migration) and networks on Matrigel (tube formation). In our hands, neither TRAIL nor FasL (1, 10, and 100 ng/ml) had an effect on parameters of angiogenesis in the HUVEC model. In hCMEC/D3 cells by contrast, TRAIL inhibited all parameters (10-100 ng/ml, 24 h). This was due to apoptosis, since its action was blocked by the pan-caspase inhibitor zVADfmk (5 x 10 -5 mol/l) and TRAIL increased caspase-3 activity 1 h after application. However FasL (100 ng/ml) increased BrdU uptake without other effects. We conclude that TRAIL has different effects on in vitro angiogenesis depending on which model is used, but that FasL is generally ineffective when applied in vitro. The data suggest that TRAIL primarily influences angiogenesis by the induction of vascular endothelial apoptosis, leading to vessel regression.

Retinoic acid-loaded polymeric nanoparticles enhance vascular regulation of neural stem cell survival and differentiation after ischaemia

Science.gov (United States)

Ferreira, R.; Fonseca, M. C.; Santos, T.; Sargento-Freitas, J.; Tjeng, R.; Paiva, F.; Castelo-Branco, M.; Ferreira, L. S.; Bernardino, L.

2016-04-01

Stroke is one of the leading causes of death and disability worldwide. However, current therapies only reach a small percentage of patients and may cause serious side effects. We propose the therapeutic use of retinoic acid-loaded nanoparticles (RA-NP) to safely and efficiently repair the ischaemic brain by creating a favourable pro-angiogenic environment that enhances neurogenesis and neuronal restitution. Our data showed that RA-NP enhanced endothelial cell proliferation and tubule network formation and protected against ischaemia-induced death. To evaluate the effect of RA-NP on vascular regulation of neural stem cell (NSC) survival and differentiation, endothelial cell-conditioned media (EC-CM) were collected. EC-CM from healthy RA-NP-treated cells reduced NSC death and promoted proliferation while EC-CM from ischaemic RA-NP-treated cells decreased cell death, increased proliferation and neuronal differentiation. In parallel, human endothelial progenitor cells (hEPC), which are part of the endogenous repair response to vascular injury, were collected from ischaemic stroke patients. hEPC treated with RA-NP had significantly higher proliferation, which further highlights the therapeutic potential of this formulation. To conclude, RA-NP protected endothelial cells from ischaemic death and stimulated the release of pro-survival, proliferation-stimulating factors and differentiation cues for NSC. RA-NP were shown to be up to 83-fold more efficient than free RA and to enhance hEPC proliferation. These data serve as a stepping stone to use RA-NP as vasculotrophic and neurogenic agents for vascular disorders and neurodegenerative diseases with compromised vasculature.

Proinflammatory Adhesion Molecules Facilitate Polychlorinated Biphenyl–Mediated Enhancement of Brain Metastasis Formation

OpenAIRE

Sipos, Eszter; Chen, Lei; András, Ibolya E.; Wrobel, Jagoda; Zhang, Bei; Pu, Hong; Park, Minseon; Eum, Sung Yong; Toborek, Michal

2012-01-01

Polychlorinated biphenyls (PCBs) are environmental toxicants that cause vascular inflammation and facilitate the development of brain metastases. The crucial event in metastasis formation is adhesion of blood-borne tumor cells to the vascular endothelium, followed by their transcapillary migration. The aim of the present study was to examine the mechanisms of PCB118-induced brain metastasis formation at the blood-brain barrier level with the focus on tumor cell adhesion to the brain endotheli...

Effects of exercise training and resveratrol on vascular health in aging

DEFF Research Database (Denmark)

Gliemann, Lasse; Nyberg, Michael Permin; Hellsten, Ylva

2016-01-01

Cardiovascular disease is a leading cause of death in the western world with aging being one of the strongest predictors of cardiovascular events. Aging is associated with impaired vascular function due to endothelial dysfunction and altered redox balance, partly caused by an increased formation ...... effects of physical activity. Regular physical activity remains the most effective way of maintaining and improving vascular health status and caution should be taken regarding potential interference of supplements on training adaptations....... of the observed detrimental effects of aging on vascular function. The effects of aging and physical activity on vascular function are, in part, related to alterations in cellular signaling through sirtuin-1, AMPK and the estrogen receptor. The polyphenol resveratrol can activate these same pathways and has......, in animals and in vitro models, been shown to act as a partial mimetic of physical activity. However, support for beneficial effects of resveratrol in human is weak and studies even show that resveratrol supplementation, similarly to supplementation with other antioxidants, can counteract the positive...

Spongiosa Primary Development: A Biochemical Hypothesis by Turing Patterns Formations

Directory of Open Access Journals (Sweden)

Oscar Rodrigo López-Vaca

2012-01-01

Full Text Available We propose a biochemical model describing the formation of primary spongiosa architecture through a bioregulatory model by metalloproteinase 13 (MMP13 and vascular endothelial growth factor (VEGF. It is assumed that MMP13 regulates cartilage degradation and the VEGF allows vascularization and advances in the ossification front through the presence of osteoblasts. The coupling of this set of molecules is represented by reaction-diffusion equations with parameters in the Turing space, creating a stable spatiotemporal pattern that leads to the formation of the trabeculae present in the spongy tissue. Experimental evidence has shown that the MMP13 regulates VEGF formation, and it is assumed that VEGF negatively regulates MMP13 formation. Thus, the patterns obtained by ossification may represent the primary spongiosa formation during endochondral ossification. Moreover, for the numerical solution, we used the finite element method with the Newton-Raphson method to approximate partial differential nonlinear equations. Ossification patterns obtained may represent the primary spongiosa formation during endochondral ossification.

Endothelial microparticles: Sophisticated vesicles modulating vascular function

Science.gov (United States)

Curtis, Anne M; Edelberg, Jay; Jonas, Rebecca; Rogers, Wade T; Moore, Jonni S; Syed, Wajihuddin; Mohler, Emile R

2015-01-01

Endothelial microparticles (EMPs) belong to a family of extracellular vesicles that are dynamic, mobile, biological effectors capable of mediating vascular physiology and function. The release of EMPs can impart autocrine and paracrine effects on target cells through surface interaction, cellular fusion, and, possibly, the delivery of intra-vesicular cargo. A greater understanding of the formation, composition, and function of EMPs will broaden our understanding of endothelial communication and may expose new pathways amenable for therapeutic manipulation. PMID:23892447

Towards the therapeutic use of vascular smooth muscle progenitor cells.

Science.gov (United States)

Merkulova-Rainon, Tatyana; Broquères-You, Dong; Kubis, Nathalie; Silvestre, Jean-Sébastien; Lévy, Bernard I

2012-07-15

Recent advances in the development of alternative proangiogenic and revascularization processes, including recombinant protein delivery, gene therapy, and cell therapy, hold the promise of greater efficacy in the management of cardiovascular disease in the coming years. In particular, vascular progenitor cell-based strategies have emerged as an efficient treatment approach to promote vessel formation and repair and to improve tissue perfusion. During the past decade, considerable progress has been achieved in understanding therapeutic properties of endothelial progenitor cells, while the therapeutic potential of vascular smooth muscle progenitor cells (SMPC) has only recently been explored; the number of the circulating SMPC being correlated with cardiovascular health. Several endogenous SMPC populations with varying phenotypes have been identified and characterized in the peripheral blood, bone marrow, and vascular wall. While the phenotypic entity of vascular SMPC is not fully defined and remains an evolving area of research, SMPC are increasingly recognized to play a special role in cardiovascular biology. In this review, we describe the current approaches used to define vascular SMPC. We further summarize the data on phenotype and functional properties of SMPC from various sources in adults. Finally, we discuss the role of SMPC in cardiovascular disease, including the contribution of SMPC to intimal proliferation, angiogenesis, and atherosclerotic plaque instability as well as the benefits resulting from the therapeutic use of SMPC.

Neural Vascular Mechanism for the Cerebral Blood Flow Autoregulation after Hemorrhagic Stroke

Directory of Open Access Journals (Sweden)

Ming Xiao

2017-01-01

Full Text Available During the initial stages of hemorrhagic stroke, including intracerebral hemorrhage and subarachnoid hemorrhage, the reflex mechanisms are activated to protect cerebral perfusion, but secondary dysfunction of cerebral flow autoregulation will eventually reduce global cerebral blood flow and the delivery of metabolic substrates, leading to generalized cerebral ischemia, hypoxia, and ultimately, neuronal cell death. Cerebral blood flow is controlled by various regulatory mechanisms, including prevailing arterial pressure, intracranial pressure, arterial blood gases, neural activity, and metabolic demand. Evoked by the concept of vascular neural network, the unveiled neural vascular mechanism gains more and more attentions. Astrocyte, neuron, pericyte, endothelium, and so forth are formed as a communicate network to regulate with each other as well as the cerebral blood flow. However, the signaling molecules responsible for this communication between these new players and blood vessels are yet to be definitively confirmed. Recent evidence suggested the pivotal role of transcriptional mechanism, including but not limited to miRNA, lncRNA, exosome, and so forth, for the cerebral blood flow autoregulation. In the present review, we sought to summarize the hemodynamic changes and underline neural vascular mechanism for cerebral blood flow autoregulation in stroke-prone state and after hemorrhagic stroke and hopefully provide more systematic and innovative research interests for the pathophysiology and therapeutic strategies of hemorrhagic stroke.

Exendin-4, a glucagon-like peptide-1 receptor agonist, reduces intimal thickening after vascular injury

Energy Technology Data Exchange (ETDEWEB)

Goto, Hiromasa [Department of Medicine, Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo 113-8421 (Japan); Nomiyama, Takashi, E-mail: tnomiyama@fukuoka-u.ac.jp [Department of Medicine, Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo 113-8421 (Japan); Mita, Tomoya; Yasunari, Eisuke; Azuma, Kosuke; Komiya, Koji; Arakawa, Masayuki; Jin, Wen Long; Kanazawa, Akio [Department of Medicine, Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo 113-8421 (Japan); Kawamori, Ryuzo [Department of Medicine, Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo 113-8421 (Japan); Sportology Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421 (Japan); Center for Therapeutic Innovations in Diabetes, Juntendo University Graduate School of Medicine, Tokyo 113-8421 (Japan); Center for Beta Cell Biology and Regeneration, Juntendo University Graduate School of Medicine, Tokyo 113-8421 (Japan); Fujitani, Yoshio; Hirose, Takahisa [Department of Medicine, Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo 113-8421 (Japan); Center for Therapeutic Innovations in Diabetes, Juntendo University Graduate School of Medicine, Tokyo 113-8421 (Japan); Watada, Hirotaka, E-mail: hwatada@juntendo.ac.jp [Department of Medicine, Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo 113-8421 (Japan); Sportology Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421 (Japan)

2011-02-04

Research highlights: {yields} Exendin-4 reduces neointimal formation after vascular injury in a mouse model. {yields} Exendin-4 dose not alter metabolic parameters in non-diabetic, non-obese mouse model. {yields} Exendin-4 reduces PDGF-induced cell proliferation in cultured SMCs. {yields} Exendin-4 may reduces neointimal formation after vascular injury at least in part through its direct action on SMCs. -- Abstract: Glucagon-like peptide-1 is a hormone secreted by L cells of the small intestine and stimulates glucose-dependent insulin response. Glucagon-like peptide-1 receptor agonists such as exendin-4 are currently used in type 2 diabetes, and considered to have beneficial effects on the cardiovascular system. To further elucidate the effect of glucagon-like peptide-1 receptor agonists on cardiovascular diseases, we investigated the effects of exendin-4 on intimal thickening after endothelial injury. Under continuous infusion of exendin-4 at 24 nmol/kg/day, C57BL/6 mice were subjected to endothelial denudation injury of the femoral artery. Treatment of mice with exendin-4 reduced neointimal formation at 4 weeks after arterial injury without altering body weight or various metabolic parameters. In addition, in vitro studies of isolated murine, rat and human aortic vascular smooth muscle cells showed the expression of GLP-1 receptor. The addition of 10 nM exendin-4 to cultured smooth muscle cells significantly reduced their proliferation induced by platelet-derived growth factor. Our results suggested that exendin-4 reduced intimal thickening after vascular injury at least in part by the suppression of platelet-derived growth factor-induced smooth muscle cells proliferation.

Exendin-4, a glucagon-like peptide-1 receptor agonist, reduces intimal thickening after vascular injury

International Nuclear Information System (INIS)

Goto, Hiromasa; Nomiyama, Takashi; Mita, Tomoya; Yasunari, Eisuke; Azuma, Kosuke; Komiya, Koji; Arakawa, Masayuki; Jin, Wen Long; Kanazawa, Akio; Kawamori, Ryuzo; Fujitani, Yoshio; Hirose, Takahisa; Watada, Hirotaka

2011-01-01

Research highlights: → Exendin-4 reduces neointimal formation after vascular injury in a mouse model. → Exendin-4 dose not alter metabolic parameters in non-diabetic, non-obese mouse model. → Exendin-4 reduces PDGF-induced cell proliferation in cultured SMCs. → Exendin-4 may reduces neointimal formation after vascular injury at least in part through its direct action on SMCs. -- Abstract: Glucagon-like peptide-1 is a hormone secreted by L cells of the small intestine and stimulates glucose-dependent insulin response. Glucagon-like peptide-1 receptor agonists such as exendin-4 are currently used in type 2 diabetes, and considered to have beneficial effects on the cardiovascular system. To further elucidate the effect of glucagon-like peptide-1 receptor agonists on cardiovascular diseases, we investigated the effects of exendin-4 on intimal thickening after endothelial injury. Under continuous infusion of exendin-4 at 24 nmol/kg/day, C57BL/6 mice were subjected to endothelial denudation injury of the femoral artery. Treatment of mice with exendin-4 reduced neointimal formation at 4 weeks after arterial injury without altering body weight or various metabolic parameters. In addition, in vitro studies of isolated murine, rat and human aortic vascular smooth muscle cells showed the expression of GLP-1 receptor. The addition of 10 nM exendin-4 to cultured smooth muscle cells significantly reduced their proliferation induced by platelet-derived growth factor. Our results suggested that exendin-4 reduced intimal thickening after vascular injury at least in part by the suppression of platelet-derived growth factor-induced smooth muscle cells proliferation.

Toward Efficient Team Formation for Crowdsourcing in Noncooperative Social Networks.

Science.gov (United States)

Wang, Wanyuan; Jiang, Jiuchuan; An, Bo; Jiang, Yichuan; Chen, Bing

2017-12-01

Crowdsourcing has become a popular service computing paradigm for requesters to integrate the ubiquitous human-intelligence services for tasks that are difficult for computers but trivial for humans. This paper focuses on crowdsourcing complex tasks by team formation in social networks (SNs) where a requester connects to a large number of workers. A good indicator of efficient team collaboration is the social connection among workers. Most previous social team formation approaches, however, either assume that the requester can maintain information of all workers and can directly communicate with them to build teams, or assume that the workers are cooperative and be willing to join the specific team built by the requester, both of which are impractical in many real situations. To this end, this paper first models each worker as a selfish entity, where the requester prefers to hire inexpensive workers that require less payment and workers prefer to join the profitable teams where they can gain high revenue. Within the noncooperative SNs, a distributed negotiation-based team formation mechanism is designed for the requester to decide which worker to hire and for the worker to decide which team to join and how much should be paid for his skill service provision. The proposed social team formation approach can always build collaborative teams by allowing team members to form a connected graph such that they can work together efficiently. Finally, we conduct a set of experiments on real dataset of workers to evaluate the effectiveness of our approach. The experimental results show that our approach can: 1) preserve considerable social welfare by comparing the benchmark centralized approaches and 2) form the profitable teams within less negotiation time by comparing the traditional distributed approaches, making our approach a more economic option for real-world applications.

VESsel GENeration Analysis (VESGEN): Innovative Vascular Mappings for Astronaut Exploration Health Risks and Human Terrestrial Medicine

Science.gov (United States)

Parsons-Wingerter, Patricia; Kao, David; Valizadegan, Hamed; Martin, Rodney; Murray, Matthew C.; Ramesh, Sneha; Sekaran, Srinivaas

2017-01-01

Currently, astronauts face significant health risks in future long-duration exploration missions such as colonizing the Moon and traveling to Mars. Numerous risks include greatly increased radiation exposures beyond the low earth orbit (LEO) of the ISS, and visual and ocular impairments in response to microgravity environments. The cardiovascular system is a key mediator in human physiological responses to radiation and microgravity. Moreover, blood vessels are necessarily involved in the progression and treatment of vascular-dependent terrestrial diseases such as cancer, coronary vessel disease, wound-healing, reproductive disorders, and diabetes. NASA developed an innovative, globally requested beta-level software, VESsel GENeration Analysis (VESGEN) to map and quantify vascular remodeling for application to astronaut and terrestrial health challenges. VESGEN mappings of branching vascular trees and networks are based on a weighted multi-parametric analysis derived from vascular physiological branching rules. Complex vascular branching patterns are determined by biological signaling mechanisms together with the fluid mechanics of multi-phase laminar blood flow.

Opinion formation models in static and dynamic social networks

Science.gov (United States)

Singh, Pramesh

We study models of opinion formation on static as well as dynamic networks where interaction among individuals is governed by widely accepted social theories. In particular, three models of competing opinions based on distinct interaction mechanisms are studied. A common feature in all of these models is the existence of a tipping point in terms of a model parameter beyond which a rapid consensus is reached. In the first model that we study on a static network, a node adopts a particular state (opinion) if a threshold fraction of its neighbors are already in that state. We introduce a few initiator nodes which are in state '1' in a population where every node is in state '0'. Thus, opinion '1' spreads through the population until no further influence is possible. Size of the spread is greatly affected by how these initiator nodes are selected. We find that there exists a critical fraction of initiators pc that is needed to trigger global cascades for a given threshold phi. We also study heuristic strategies for selecting a set of initiator nodes in order to maximize the cascade size. The structural properties of networks also play an important role in the spreading process. We study how the dynamics is affected by changing the clustering in a network. It turns out that local clustering is helpful in spreading. Next, we studied a model where the network is dynamic and interactions are homophilic. We find that homophily-driven rewiring impedes the reaching of consensus and in the absence of committed nodes (nodes that are not influenceable on their opinion), consensus time Tc diverges exponentially with network size N . As we introduce a fraction of committed nodes, beyond a critical value, the scaling of Tc becomes logarithmic in N. We also find that slight change in the interaction rule can produce strikingly different scaling behaviors of T c . However, introducing committed agents in the system drastically improves the scaling of the consensus time regardless of

Therapeutic Interference With Vascular Calcification—Lessons From Klotho-Hypomorphic Mice and Beyond

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Florian Lang

2018-05-01

Full Text Available Medial vascular calcification, a major pathophysiological process associated with cardiovascular disease and mortality, involves osteo-/chondrogenic transdifferentiation of vascular smooth muscle cells (VSMCs. In chronic kidney disease (CKD, osteo-/chondrogenic transdifferentiation of VSMCs and, thus, vascular calcification is mainly driven by hyperphosphatemia, resulting from impaired elimination of phosphate by the diseased kidneys. Hyperphosphatemia with subsequent vascular calcification is a hallmark of klotho-hypomorphic mice, which are characterized by rapid development of multiple age-related disorders and early death. In those animals, hyperphosphatemia results from unrestrained formation of 1,25(OH2D3 with subsequent retention of calcium and phosphate. Analysis of klotho-hypomorphic mice and mice with vitamin D3 overload uncovered several pathophysiological mechanisms participating in the orchestration of vascular calcification and several therapeutic opportunities to delay or even halt vascular calcification. The present brief review addresses the beneficial effects of bicarbonate, carbonic anhydrase inhibition, magnesium supplementation, mineralocorticoid receptor (MR blockage, and ammonium salts. The case is made that bicarbonate is mainly effective by decreasing intestinal phosphate absorption, and that carbonic anhydrase inhibition leads to metabolic acidosis, which counteracts calcium-phosphate precipitation and VSMC transdifferentiation. Magnesium supplementation, MR blockage and ammonium salts are mainly effective by interference with osteo-/chondrogenic signaling in VSMCs. It should be pointed out that the, by far, most efficient substances are ammonium salts, which may virtually prevent vascular calcification. Future research will probably uncover further therapeutic options and, most importantly, reveal whether these observations in mice can be translated into treatment of patients suffering from vascular calcification, such

Suppressions of Serotonin-Induced Increased Vascular Permeability and Leukocyte Infiltration by Bixa orellana Leaf Extract

Directory of Open Access Journals (Sweden)

Yoke Keong Yong

2013-01-01

Full Text Available The aim of the present study was to evaluate the anti-inflammatory activities of aqueous extract of Bixa orellana (AEBO leaves and its possible mechanisms in animal models. The anti-inflammatory activity of the extract was evaluated using serotonin-induced rat paw edema, increased peritoneal vascular permeability, and leukocyte infiltrations in an air-pouch model. Nitric oxide (NO, indicated by the sum of nitrites and nitrates, and vascular growth endothelial growth factor (VEGF were measured in paw tissues of rats to determine their involvement in the regulation of increased permeability. Pretreatments with AEBO (50 and 150 mg kg−1 prior to serotonin inductions resulted in maximum inhibitions of 56.2% of paw volume, 45.7% of Evans blue dye leakage in the peritoneal vascular permeability model, and 83.9% of leukocyte infiltration in the air-pouch model. 57.2% maximum inhibition of NO and 27% of VEGF formations in rats’ paws were observed with AEBO at the dose of 150 mg kg−1. Pharmacological screening of the extract showed significant (P<0.05 anti-inflammatory activity, indicated by the suppressions of increased vascular permeability and leukocyte infiltration. The inhibitions of these inflammatory events are probably mediated via inhibition of NO and VEGF formation and release.

Pediatric vascular access

International Nuclear Information System (INIS)

Donaldson, James S.

2006-01-01

Pediatric interventional radiologists are ideally suited to provide vascular access services to children because of inherent safety advantages and higher success from using image-guided techniques. The performance of vascular access procedures has become routine at many adult interventional radiology practices, but this service is not as widely developed at pediatric institutions. Although interventional radiologists at some children's hospitals offer full-service vascular access, there is little or none at others. Developing and maintaining a pediatric vascular access service is a challenge. Interventionalists skilled in performing such procedures are limited at pediatric institutions, and institutional support from clerical staff, nursing staff, and technologists might not be sufficiently available to fulfill the needs of such a service. There must also be a strong commitment by all members of the team to support such a demanding service. There is a slippery slope of expected services that becomes steeper and steeper as the vascular access service grows. This review is intended primarily as general education for pediatric radiologists learning vascular access techniques. Additionally, the pediatric or adult interventional radiologist seeking to expand services might find helpful tips. The article also provides education for the diagnostic radiologist who routinely interprets radiographs containing vascular access devices. (orig.)

Domain wall network as QCD vacuum and the chromomagnetic trap formation under extreme conditions

International Nuclear Information System (INIS)

Nedelko, Sergei N.; Voronin, Vladimir E.

2015-01-01

The ensemble of Euclidean gluon field configurations represented by the domain wall network is considered. A single domain wall is given by the sine-Gordon kink for the angle between chromomagnetic and chromoelectric components of the gauge field. The domain wall separates the regions with Abelian self-dual and anti-self-dual fields. The network of the domain wall defects is introduced as a combination of multiplicative and additive superpositions of kinks. The character of the spectrum and eigenmodes of color-charged fluctuations in the presence of the domain wall network is discussed. Conditions for the formation of a stable thick domain wall junction (the chromomagnetic trap) during heavy-ion collisions are discussed, and the spectrum of color-charged quasi-particles inside the trap is evaluated. An important observation is the existence of the critical size L c of a single trap stable against gluon tachyonic modes. The size L c is related to the value of gluon condensate left angle g 2 F 2 right angle. The growth of large lumps of merged chromomagnetic traps and the concept of the confinement-deconfinement transition in terms of the ensemble of domain wall networks are outlined. (orig.)

High wall shear stress and spatial gradients in vascular pathology: a review.

Science.gov (United States)

Dolan, Jennifer M; Kolega, John; Meng, Hui

2013-07-01

Cardiovascular pathologies such as intracranial aneurysms (IAs) and atherosclerosis preferentially localize to bifurcations and curvatures where hemodynamics are complex. While extensive knowledge about low wall shear stress (WSS) has been generated in the past, due to its strong relevance to atherogenesis, high WSS (typically >3 Pa) has emerged as a key regulator of vascular biology and pathology as well, receiving renewed interests. As reviewed here, chronic high WSS not only stimulates adaptive outward remodeling, but also contributes to saccular IA formation (at bifurcation apices or outer curves) and atherosclerotic plaque destabilization (in stenosed vessels). Recent advances in understanding IA pathogenesis have shed new light on the role of high WSS in pathological vascular remodeling. In complex geometries, high WSS can couple with significant spatial WSS gradient (WSSG). A combination of high WSS and positive WSSG has been shown to trigger aneurysm initiation. Since endothelial cells (ECs) are sensors of WSS, we have begun to elucidate EC responses to high WSS alone and in combination with WSSG. Understanding such responses will provide insight into not only aneurysm formation, but also plaque destabilization and other vascular pathologies and potentially lead to improved strategies for disease management and novel targets for pharmacological intervention.

Formation of hybrid gold nanoparticle network aggregates by specific host-guest interactions in a turbulent flow reactor

NARCIS (Netherlands)

Weinhart-Mejia, R.; Huskens, Jurriaan

2014-01-01

A multi-inlet vortex mixer (MIVM) was used to investigate the formation of hybrid gold nanoparticle network aggregates under highly turbulent flow conditions. To form aggregates, gold nanoparticles were functionalized with β-cyclodextrin (CD) and mixed with adamantyl (Ad)-terminated

Surface modification and endothelialization of biomaterials as potential scaffolds for vascular tissue engineering applications.

Science.gov (United States)

Ren, Xiangkui; Feng, Yakai; Guo, Jintang; Wang, Haixia; Li, Qian; Yang, Jing; Hao, Xuefang; Lv, Juan; Ma, Nan; Li, Wenzhong

2015-08-07

Surface modification and endothelialization of vascular biomaterials are common approaches that are used to both resist the nonspecific adhesion of proteins and improve the hemocompatibility and long-term patency of artificial vascular grafts. Surface modification of vascular grafts using hydrophilic poly(ethylene glycol), zwitterionic polymers, heparin or other bioactive molecules can efficiently enhance hemocompatibility, and consequently prevent thrombosis on artificial vascular grafts. However, these modified surfaces may be excessively hydrophilic, which limits initial vascular endothelial cell adhesion and formation of a confluent endothelial lining. Therefore, the improvement of endothelialization on these grafts by chemical modification with specific peptides and genes is now arousing more and more interest. Several active peptides, such as RGD, CAG, REDV and YIGSR, can be specifically recognized by endothelial cells. Consequently, graft surfaces that are modified by these peptides can exhibit targeting selectivity for the adhesion of endothelial cells, and genes can be delivered by targeting carriers to specific tissues to enhance the promotion and regeneration of blood vessels. These methods could effectively accelerate selective endothelial cell recruitment and functional endothelialization. In this review, recent developments in the surface modification and endothelialization of biomaterials in vascular tissue engineering are summarized. Both gene engineering and targeting ligand immobilization are promising methods to improve the clinical outcome of artificial vascular grafts.

Use of formative research and social network theory to develop a group walking intervention: Sumter County on the Move!

Science.gov (United States)

Forthofer, Melinda; Burroughs-Girardi, Ericka; Stoisor-Olsson, Liliana; Wilcox, Sara; Sharpe, Patricia A; Pekuri, Linda M

2016-10-01

Although social support is a frequently cited enabler of physical activity, few studies have examined how to harness social support in interventions. This paper describes community-based formative research to design a walking program for mobilizing naturally occurring social networks to support increases in walking behavior. Focus group methods were used to engage community members in discussions about desired walking program features. The research was conducted with underserved communities in Sumter County, South Carolina. The majority of focus group participants were women (76%) and African American (92%). Several important themes emerged from the focus group results regarding attitudes toward walking, facilitators of and barriers to walking, ideal walking program characteristics, and strategies for encouraging community members to walk. Most noteably, the role of existing social networks as a supportive influence on physical activity was a recurring theme in our formative research and a gap in the existing evidence base. The resulting walking program focused on strategies for mobilizing, supporting and reinforcing existing social networks as mechanisms for increasing walking. Our approach to linking theory, empirical evidence and community-based formative research for the development of a walking intervention offers an example for practitioners developing intervention strategies for a wide range of behaviors. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hepatocyte growth factor triggers signaling cascades mediating vascular smooth muscle cell migration

NARCIS (Netherlands)

Taher, Taher E. I.; Derksen, Patrick W. B.; de Boer, Onno J.; Spaargaren, Marcel; Teeling, Peter; van der Wal, Allard C.; Pals, Steven T.

2002-01-01

A key event in neointima formation and atherogenesis is the migration of vascular smooth muscle cells (VSMCs) into the intima. This is controlled by cytokines and extracellular matix (ECM) components within the microenvironment of the diseased vessel wall. At present, these signals have only been

Data format translation routines

International Nuclear Information System (INIS)

Burris, R.D.

1981-02-01

To enable the effective connection of several dissimilar computers into a network, modification of the data being passed from one computer to another may become necessary. This document describes a package of routines which permit the translation of data in PDP-8 formats to PDP-11 or DECsystem-10 formats or from PDP-11 format to DECsystem-10 format. Additional routines are described which permit the effective use of the translation routines in the environment of the Fusion Energy Division (FED) network and the Elmo Bumpy Torus (EBT) data base

Brains striving for coherence: Long-term cumulative plot formation in the default mode network.

Science.gov (United States)

Tylén, K; Christensen, P; Roepstorff, A; Lund, T; Østergaard, S; Donald, M

2015-11-01

Many everyday activities, such as engaging in conversation or listening to a story, require us to sustain attention over a prolonged period of time while integrating and synthesizing complex episodic content into a coherent mental model. Humans are remarkably capable of navigating and keeping track of all the parallel social activities of everyday life even when confronted with interruptions or changes in the environment. However, the underlying cognitive and neurocognitive mechanisms of such long-term integration and profiling of information remain a challenge to neuroscience. While brain activity is generally traceable within the short time frame of working memory (milliseconds to seconds), these integrative processes last for minutes, hours or even days. Here we report two experiments on story comprehension. Experiment I establishes a cognitive dissociation between our comprehension of plot and incidental facts in narratives: when episodic material allows for long-term integration in a coherent plot, we recall fewer factual details. However, when plot formation is challenged, we pay more attention to incidental facts. Experiment II investigates the neural underpinnings of plot formation. Results suggest a central role for the brain's default mode network related to comprehension of coherent narratives while incoherent episodes rather activate the frontoparietal control network. Moreover, an analysis of cortical activity as a function of the cumulative integration of narrative material into a coherent story reveals to linear modulations of right hemisphere posterior temporal and parietal regions. Together these findings point to key neural mechanisms involved in the fundamental human capacity for cumulative plot formation. Copyright © 2015 Elsevier Inc. All rights reserved.

Risk aversion and social networks

NARCIS (Netherlands)

Kovarik, J.; van der Leij, M.J.

2011-01-01

Agents involved in the formation of a social or economic network typically face uncertainty about the benefits of creating a link. However, the interplay of such uncertainty and risk attitudes has been neglected in the network formation literature. We propose a dynamic network formation model that

Risk aversion and social networks

NARCIS (Netherlands)

Kovářík, J.; van der Leij, M.J.

2012-01-01

Agents involved in the formation of a social or economic network typically face uncertainty about the benefits of creating a link. However, the interplay of such uncertainty and risk attitudes has been neglected in the network formation literature. We propose a dynamic network formation model that

Experimental demonstration of large capacity WSDM optical access network with multicore fibers and advanced modulation formats.

Science.gov (United States)

Li, Borui; Feng, Zhenhua; Tang, Ming; Xu, Zhilin; Fu, Songnian; Wu, Qiong; Deng, Lei; Tong, Weijun; Liu, Shuang; Shum, Perry Ping

2015-05-04

Towards the next generation optical access network supporting large capacity data transmission to enormous number of users covering a wider area, we proposed a hybrid wavelength-space division multiplexing (WSDM) optical access network architecture utilizing multicore fibers with advanced modulation formats. As a proof of concept, we experimentally demonstrated a WSDM optical access network with duplex transmission using our developed and fabricated multicore (7-core) fibers with 58.7km distance. As a cost-effective modulation scheme for access network, the optical OFDM-QPSK signal has been intensity modulated on the downstream transmission in the optical line terminal (OLT) and it was directly detected in the optical network unit (ONU) after MCF transmission. 10 wavelengths with 25GHz channel spacing from an optical comb generator are employed and each wavelength is loaded with 5Gb/s OFDM-QPSK signal. After amplification, power splitting, and fan-in multiplexer, 10-wavelength downstream signal was injected into six outer layer cores simultaneously and the aggregation downstream capacity reaches 300 Gb/s. -16 dBm sensitivity has been achieved for 3.8 × 10-3 bit error ratio (BER) with 7% Forward Error Correction (FEC) limit for all wavelengths in every core. Upstream signal from ONU side has also been generated and the bidirectional transmission in the same core causes negligible performance degradation to the downstream signal. As a universal platform for wired/wireless data access, our proposed architecture provides additional dimension for high speed mobile signal transmission and we hence demonstrated an upstream delivery of 20Gb/s per wavelength with QPSK modulation formats using the inner core of MCF emulating a mobile backhaul service. The IQ modulated data was coherently detected in the OLT side. -19 dBm sensitivity has been achieved under the FEC limit and more than 18 dB power budget is guaranteed.

Connections matter: channeled hydrogels to improve vascularization.

Science.gov (United States)

Muehleder, Severin; Ovsianikov, Aleksandr; Zipperle, Johannes; Redl, Heinz; Holnthoner, Wolfgang

2014-01-01

The use of cell-laden hydrogels to engineer soft tissue has been emerging within the past years. Despite, several newly developed and sophisticated techniques to encapsulate different cell types the importance of vascularization of the engineered constructs is often underestimated. As a result, cell death within a construct leads to impaired function and inclusion of the implant. Here, we discuss the fabrication of hollow channels within hydrogels as a promising strategy to facilitate vascularization. Furthermore, we present an overview on the feasible use of removable spacers, 3D laser-, and planar processing strategies to create channels within hydrogels. The implementation of these structures promotes control over cell distribution and increases oxygen transport and nutrient supply in vitro. However, many studies lack the use of endothelial cells in their approaches leaving out an important factor to enhance vessel ingrowth and anastomosis formation upon implantation. In addition, the adequate endothelial cell type needs to be considered to make these approaches bridge the gap to in vivo applications.

Sticky or Slippery Wetting: Network Formation Conditions Can Provide a One-Way Street for Water Flow on Platinum-cured Silicone.

Science.gov (United States)

Wang, Chenyu; Nair, Sithara S; Veeravalli, Sharon; Moseh, Patricia; Wynne, Kenneth J

2016-06-08

In the course of studies on Sylgard 184 (S-PDMS), we discovered strong effects on receding contact angles (CAs), θrec, while cure conditions have little effect on advancing CAs. Network formation at high temperatures resulted in high θadv of 115-120° and high θrec ≥ 80°. After network formation at low temperatures (≤25 °C), θadv was still high but θrec was 30-50°. Uncertainty about compositional effects on wetting behavior resulted in similar experiments with a model D(V)D(H) silicone elastomer (Pt-PDMS) composed of a vinyl-terminated poly(dimethylsiloxane) (PDMS) base and a polymeric hydromethylsilane cross-linker. Again, network formation at high temperature (∼100 °C) resulted in high CAs, while low-temperature curing retained high advancing CAs but gave low receding CAs (θrec 30-50°). These changes in receding CAs translate to strong effects on water adhesion, wp, which is the actual work required to separate a liquid (water) from a surface: wp ∝ (1 + θrec). When the values θrec 84° for high-temperature and θrec 50° for low-temperature network formation are used, wp is ∼1.5 times higher for curing at low temperature. The origin of low receding contact angles was investigated by attenuated total reflectance IR spectroscopy. Absorptions for Si-OH hydrogen-bonded to water (3350 cm(-1)) were stronger for low- versus high-temperature curing. This result is attributed to faster hydrosilylation during curing at higher temperatures that consumes Si-H before autoxidation to Si-OH. Sharp bands at 3750 and 3690 cm(-1) due to isolated -Si-OH are more prominent for Pt-PDMS than those for S-PDMS, which may be due to an effect of functionalized nanofiller. To explore the impact of wp on water droplet flow, gradient coatings of S-PDMS and Pt-PDMS elastomers were prepared by coating a slide, maintaining opposite ends at high and low temperatures and thus forming a thermal gradient. When the slide was tilted, a droplet moved easily on the high

Magnesium Counteracts Vascular Calcification: Passive Interference or Active Modulation?

Science.gov (United States)

Ter Braake, Anique D; Shanahan, Catherine M; de Baaij, Jeroen H F

2017-08-01

Over the last decade, an increasing number of studies report a close relationship between serum magnesium concentration and cardiovascular disease risk in the general population. In end-stage renal disease, an association was found between serum magnesium and survival. Hypomagnesemia was identified as a strong predictor for cardiovascular disease in these patients. A substantial body of in vitro and in vivo studies has identified a protective role for magnesium in vascular calcification. However, the precise mechanisms and its contribution to cardiovascular protection remain unclear. There are currently 2 leading hypotheses: first, magnesium may bind phosphate and delay calcium phosphate crystal growth in the circulation, thereby passively interfering with calcium phosphate deposition in the vessel wall. Second, magnesium may regulate vascular smooth muscle cell transdifferentiation toward an osteogenic phenotype by active cellular modulation of factors associated with calcification. Here, the data supporting these major hypotheses are reviewed. The literature supports both a passive inorganic phosphate-buffering role reducing hydroxyapatite formation and an active cell-mediated role, directly targeting vascular smooth muscle transdifferentiation. However, current evidence relies on basic experimental designs that are often insufficient to delineate the underlying mechanisms. The field requires more advanced experimental design, including determination of intracellular magnesium concentrations and the identification of the molecular players that regulate magnesium concentrations in vascular smooth muscle cells. © 2017 American Heart Association, Inc.

Vascular Access in Children

International Nuclear Information System (INIS)

Krishnamurthy, Ganesh; Keller, Marc S.

2011-01-01

Establishment of stable vascular access is one of the essential and most challenging procedures in a pediatric hospital. Many clinical specialties provide vascular service in a pediatric hospital. At the top of the “expert procedural pyramid” is the pediatric interventional radiologist, who is best suited and trained to deliver this service. Growing awareness regarding the safety and high success rate of vascular access using image guidance has led to increased demand from clinicians to provide around-the-clock vascular access service by pediatric interventional radiologists. Hence, the success of a vascular access program, with the pediatric interventional radiologist as the key provider, is challenging, and a coordinated multidisciplinary team effort is essential for success. However, there are few dedicated pediatric interventional radiologists across the globe, and also only a couple of training programs exist for pediatric interventions. This article gives an overview of the technical aspects of pediatric vascular access and provides useful tips for obtaining vascular access in children safely and successfully using image guidance.

Interstitial fluid flow and drug delivery in vascularized tumors: a computational model.

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Michael Welter

Full Text Available Interstitial fluid is a solution that bathes and surrounds the human cells and provides them with nutrients and a way of waste removal. It is generally believed that elevated tumor interstitial fluid pressure (IFP is partly responsible for the poor penetration and distribution of therapeutic agents in solid tumors, but the complex interplay of extravasation, permeabilities, vascular heterogeneities and diffusive and convective drug transport remains poorly understood. Here we consider-with the help of a theoretical model-the tumor IFP, interstitial fluid flow (IFF and its impact upon drug delivery within tumor depending on biophysical determinants such as vessel network morphology, permeabilities and diffusive vs. convective transport. We developed a vascular tumor growth model, including vessel co-option, regression, and angiogenesis, that we extend here by the interstitium (represented by a porous medium obeying Darcy's law and sources (vessels and sinks (lymphatics for IFF. With it we compute the spatial variation of the IFP and IFF and determine its correlation with the vascular network morphology and physiological parameters like vessel wall permeability, tissue conductivity, distribution of lymphatics etc. We find that an increased vascular wall conductivity together with a reduction of lymph function leads to increased tumor IFP, but also that the latter does not necessarily imply a decreased extravasation rate: Generally the IF flow rate is positively correlated with the various conductivities in the system. The IFF field is then used to determine the drug distribution after an injection via a convection diffusion reaction equation for intra- and extracellular concentrations with parameters guided by experimental data for the drug Doxorubicin. We observe that the interplay of convective and diffusive drug transport can lead to quite unexpected effects in the presence of a heterogeneous, compartmentalized vasculature. Finally we discuss

Interstitial fluid flow and drug delivery in vascularized tumors: a computational model.

Science.gov (United States)

Welter, Michael; Rieger, Heiko

2013-01-01

Interstitial fluid is a solution that bathes and surrounds the human cells and provides them with nutrients and a way of waste removal. It is generally believed that elevated tumor interstitial fluid pressure (IFP) is partly responsible for the poor penetration and distribution of therapeutic agents in solid tumors, but the complex interplay of extravasation, permeabilities, vascular heterogeneities and diffusive and convective drug transport remains poorly understood. Here we consider-with the help of a theoretical model-the tumor IFP, interstitial fluid flow (IFF) and its impact upon drug delivery within tumor depending on biophysical determinants such as vessel network morphology, permeabilities and diffusive vs. convective transport. We developed a vascular tumor growth model, including vessel co-option, regression, and angiogenesis, that we extend here by the interstitium (represented by a porous medium obeying Darcy's law) and sources (vessels) and sinks (lymphatics) for IFF. With it we compute the spatial variation of the IFP and IFF and determine its correlation with the vascular network morphology and physiological parameters like vessel wall permeability, tissue conductivity, distribution of lymphatics etc. We find that an increased vascular wall conductivity together with a reduction of lymph function leads to increased tumor IFP, but also that the latter does not necessarily imply a decreased extravasation rate: Generally the IF flow rate is positively correlated with the various conductivities in the system. The IFF field is then used to determine the drug distribution after an injection via a convection diffusion reaction equation for intra- and extracellular concentrations with parameters guided by experimental data for the drug Doxorubicin. We observe that the interplay of convective and diffusive drug transport can lead to quite unexpected effects in the presence of a heterogeneous, compartmentalized vasculature. Finally we discuss various

Use of gold nanoparticles to detect water uptake in vascular plants.

Science.gov (United States)

Hwang, Bae Geun; Ahn, Sungsook; Lee, Sang Joon

2014-01-01

Direct visualization of water-conducting pathways and sap flows in xylem vessels is important for understanding the physiology of vascular plants and their sap ascent. Gold nanoparticles (AuNPs) combined with synchrotron X-ray imaging technique is a new promising tool for investigating plant hydraulics in opaque xylem vessels of vascular plants. However, in practical applications of AuNPs for real-time quantitative visualization of sap flows, their interaction with a vascular network needs to be verified in advance. In this study, the effect of AuNPs on the water-refilling function of xylem vessels is experimentally investigated with three monocot species. Discrepancy in the water uptakes starts to appear at about 20 min to 40 min after the supply of AuNP solution to the test plant by the possible gradual accumulation of AuNPs on the internal structures of vasculature. However conclusively, it is observed that the water-refilling speeds in individual xylem vessels are virtually unaffected by hydrophilically surface-modified AuNPs (diameter ∼20 nm). Therefore, the AuNPs can be effectively used as flow tracers in the xylem vessels in the first 20∼30 min without any physiological barrier. As a result, AuNPs are found to be useful for visualizing various fluid dynamic phenomena occurring in vascular plants.

The behavior of the vascular system in the experimental tumor radiotherapy

International Nuclear Information System (INIS)

Yamaura, Hirotsugu; Matsuzawa, Taiju; Sato, Haruo; Ito, Yasuhiko.

1975-01-01

The rat ascites hepatoma AH109A transplanted and grown in the rat transparent chamber developed a tumor specific vascular system, the process of which was quantitatively studied because of the vascular length, surface area, and volume per mm 3 of tissue. The values changed characteristically in each stage of the course. The tumor was irradiated in a chamber with 3000 R of 60 Co γ-rays, and the tumor cells died leaving behind highly dense capillary networks, which gradually returned to normal level by 7 days after irradiation. The blood vessels, either preformed or newly formed, in the control tissue without tumor were not damaged by this dose. But the proliferation of capillary buds were inhibited slightly with 400 R and completely with 4000 R. (auth.)

Revascularization of femoral head ischemic necrosis with vascularized bone graft: A CT scan experimental study

International Nuclear Information System (INIS)

Gonzalez del Pino, J.; Knapp, K.; Gomez Castresana, F.; Benito, M.

1990-01-01

An ischemic necrosis of the femoral head was induced in 15 mongrel adult dogs using the technique described by Gartsman et al. Five weeks later, a free vascularized rib graft was transferred into the previously induced ischemic femoral head. High resolution computed tomographic scanning was used to evaluate revascularization 4, 8 and 12 weeks after grafting. The femoral head exhibited new vessel formation throughout the study. Arterial terminal branches arising from the rib graft medullary and periosteal circulations extended beyond the rib graft, entered the head, and reached the subchondral plate. Even where the rib graft did not replenish the central core of the head, there was vascular supply from the grafted bone's vascular tree. These results suggest that a free vascularized bone graft is able to revascularize an experimentally induced ischemic femoral head necrosis. (orig.)

Oscillation of Angiogenesis and Vascular Dropout in Progressive Human Vascular Disease. [Vascular Pattern as Useful Read-Out of Complex Molecular Signaling

Science.gov (United States)

Parsons-Wingerter, Patricia

2010-01-01

When analyzed by VESsel GENeration Analysis (VESGEN) software, vascular patterns provide useful integrative read-outs of complex, interacting molecular signaling pathways. Using VESGEN, we recently discovered and published our innovative, surprising findings that angiogenesis oscillated with vascular dropout throughout progression of diabetic retinopathy, a blinding vascular disease. Our findings provide a potential paradigm shift in the current prevailing view on progression and treatment of this disease, and a new early-stage window of regenerative therapeutic opportunities. The findings also suggest that angiogenesis may oscillate with vascular disease in a homeostatic-like manner during early stages of other inflammatory progressive diseases such as cancer and coronary vascular disease.

Distributed Adaptive Finite-Time Approach for Formation-Containment Control of Networked Nonlinear Systems Under Directed Topology.

Science.gov (United States)

Wang, Yujuan; Song, Yongduan; Ren, Wei

2017-07-06

This paper presents a distributed adaptive finite-time control solution to the formation-containment problem for multiple networked systems with uncertain nonlinear dynamics and directed communication constraints. By integrating the special topology feature of the new constructed symmetrical matrix, the technical difficulty in finite-time formation-containment control arising from the asymmetrical Laplacian matrix under single-way directed communication is circumvented. Based upon fractional power feedback of the local error, an adaptive distributed control scheme is established to drive the leaders into the prespecified formation configuration in finite time. Meanwhile, a distributed adaptive control scheme, independent of the unavailable inputs of the leaders, is designed to keep the followers within a bounded distance from the moving leaders and then to make the followers enter the convex hull shaped by the formation of the leaders in finite time. The effectiveness of the proposed control scheme is confirmed by the simulation.

Sost Deficiency does not Alter Bone’s Lacunar or Vascular Porosity in Mice

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Henry Mosey

2017-09-01

Full Text Available SCLEROSTIN (Sost is expressed predominantly in osteocytes acting as a negative regulator of bone formation. In humans, mutations in the SOST gene lead to skeletal overgrowth and increased bone mineral density, suggesting that SCLEROSTIN is a key regulator of bone mass. The function of SCLEROSTIN as an inhibitor of bone formation is further supported by Sost knockout (KO mice which display a high bone mass with elevated bone formation. Previous studies have indicated that Sost exerts its effect on bone formation through Wnt-mediated regulation of osteoblast differentiation, proliferation, and activity. Recent in vitro studies have also suggested that SCLEROSTIN regulates angiogenesis and osteoblast-to-osteocyte transition. Despite this wealth of knowledge of the mechanisms responsible for SCLEROSTIN action, no previous studies have examined whether SCLEROSTIN regulates osteocyte and vascular configuration in cortices of mouse tibia. Herein, we image tibiae from Sost KO mice and their wild-type (WT counterparts with high-resolution CT to examine whether lack of SCLEROSTIN influences the morphometric properties of lacunae and vascular canal porosity relating to osteocytes and vessels within cortical bone. Male Sost KO and WT mice (n = 6/group were sacrificed at 12 weeks of age. Fixed tibiae were analyzed using microCT to examine cortical bone mass and architecture. Then, samples were imaged by using benchtop and synchrotron nano-computed tomography at the tibiofibular junction. Our data, consistent with previous studies show that, Sost deficiency leads to significant enhancement of bone mass by cortical thickening and bigger cross-sectional area and we find that this occurs without modifications of tibial ellipticity, a measure of bone shape. In addition, our data show that there are no significant differences in any lacunar or vascular morphometric or geometric parameters between Sost KO mouse tibia and WT counterparts. We, therefore

Divergent effects of 17-β-estradiol on human vascular smooth muscle and endothelial cell function diminishes TNF-α-induced neointima formation

International Nuclear Information System (INIS)

Nintasen, Rungrat; Riches, Kirsten; Mughal, Romana S.; Viriyavejakul, Parnpen; Chaisri, Urai; Maneerat, Yaowapa; Turner, Neil A.; Porter, Karen E.

2012-01-01

Highlights: ► TNF-α augments neointimal hyperplasia in human saphenous vein. ► TNF-α induces detrimental effects on endothelial and smooth muscle cell function. ► Estradiol exerts modulatory effects on TNF-induced vascular cell functions. ► The modulatory effects of estradiol are discriminatory and cell-type specific. -- Abstract: Coronary heart disease (CHD) is a condition characterized by increased levels of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α). TNF-α can induce vascular endothelial cell (EC) and smooth muscle cell (SMC) dysfunction, central events in development of neointimal lesions. The reduced incidence of CHD in young women is believed to be due to the protective effects of estradiol (E2). We therefore investigated the effects of TNF-α on human neointima formation and SMC/EC functions and any modulatory effects of E2. Saphenous vein (SV) segments were cultured in the presence of TNF-α (10 ng/ml), E2 (2.5 nM) or both in combination. Neointimal thickening was augmented by incubation with TNF-α, an effect that was abolished by co-culture with E2. TNF-α increased SV–SMC proliferation in a concentration-dependent manner that was optimal at 10 ng/ml (1.5-fold increase), and abolished by E2 at all concentrations studied (1–50 nM). Surprisingly, E2 itself at low concentrations (1 and 5 nM) stimulated SV–SMC proliferation to a level comparable to that of TNF-α alone. SV–EC migration was significantly impaired by TNF-α (42% of control), and co-culture with E2 partially restored the ability of SV–EC to migrate and repair the wound. In contrast, TNF-α increased SV–SMC migration by 1.7-fold, an effect that was completely reversed by co-incubation with E2. Finally, TNF-α potently induced ICAM-1 and VCAM-1 expression in both SV–EC and SV–SMC. However there was no modulation by E2 in either cell-type. In conclusion, TNF-α induced SV neointima formation, increased SMC proliferation and migration, impaired

Formation of Neural Networks in 3D Scaffolds Fabricated by Means of Laser Microstereolithography.

Science.gov (United States)

Vedunova, M V; Timashev, P S; Mishchenko, T A; Mitroshina, E V; Koroleva, A V; Chichkov, B N; Panchenko, V Ya; Bagratashvili, V N; Mukhina, I V

2016-08-01

We developed and tested new 3D scaffolds for neurotransplantation. Scaffolds of predetermined architectonic were prepared using microstereolithography technique. Scaffolds were highly biocompatible with the nervous tissue cells. In vitro studies showed that the material of fabricated scaffolds is not toxic for dissociated brain cells and promotes the formation of functional neural networks in the matrix. These results demonstrate the possibility of fabrication of tissue-engineering constructs for neurotransplantation based on created scaffolds.

Linear approximation model network and its formation via ...

Indian Academy of Sciences (India)

To overcome the deficiency of `local model network' (LMN) techniques, an alternative `linear approximation model' (LAM) network approach is proposed. Such a network models a nonlinear or practical system with multiple linear models fitted along operating trajectories, where individual models are simply networked ...

[Vascular Calcification - Pathological Mechanism and Clinical Application - . Role of vascular smooth muscle cells in vascular calcification].

Science.gov (United States)

Kurabayashi, Masahiko

2015-05-01

Vascular calcification is commonly seen with aging, chronic kidney disese (CKD), diabetes, and atherosclerosis, and is closely associated with cardiovascular morbidity and mortality. Vascular calcification has long been regarded as the final stage of degeneration and necrosis of arterial wall and a passive, unregulated process. However, it is now known to be an active and tightly regulated process involved with phenotypic transition of vascular smooth muscle cells (VSMC) that resembles bone mineralization. Briefly, calcium deposits of atherosclerotic plaque consist of hydroxyapatite and may appear identical to fully formed lamellar bone. By using a genetic fate mapping strategy, VSMC of the vascular media give rise to the majority of the osteochondrogenic precursor- and chondrocyte-like cells observed in the calcified arterial media of MGP (- / -) mice. Osteogenic differentiation of VSMC is characterized by the expression of bone-related molecules including bone morphogenetic protein (BMP) -2, Msx2 and osteopontin, which are produced by osteoblasts and chondrocytes. Our recent findings are that (i) Runx2 and Notch1 induce osteogenic differentiation, and (ii) advanced glycation end-product (AGE) /receptor for AGE (RAGE) and palmitic acid promote osteogenic differentiation of VSMC. To understand of the molecular mechanisms of vascular calcification is now under intensive research area.

Neutrophil Extracellular Trap-Related Extracellular Histones Cause Vascular Necrosis in Severe GN.

Science.gov (United States)

Kumar, Santhosh V R; Kulkarni, Onkar P; Mulay, Shrikant R; Darisipudi, Murthy N; Romoli, Simone; Thomasova, Dana; Scherbaum, Christina R; Hohenstein, Bernd; Hugo, Christian; Müller, Susanna; Liapis, Helen; Anders, Hans-Joachim

2015-10-01

Severe GN involves local neutrophil extracellular trap (NET) formation. We hypothesized a local cytotoxic effect of NET-related histone release in necrotizing GN. In vitro, histones from calf thymus or histones released by neutrophils undergoing NETosis killed glomerular endothelial cells, podocytes, and parietal epithelial cells in a dose-dependent manner. Histone-neutralizing agents such as antihistone IgG, activated protein C, or heparin prevented this effect. Histone toxicity on glomeruli ex vivo was Toll-like receptor 2/4 dependent, and lack of TLR2/4 attenuated histone-induced renal thrombotic microangiopathy and glomerular necrosis in mice. Anti-glomerular basement membrane GN involved NET formation and vascular necrosis, whereas blocking NET formation by peptidylarginine inhibition or preemptive anti-histone IgG injection significantly reduced all aspects of GN (i.e., vascular necrosis, podocyte loss, albuminuria, cytokine induction, recruitment or activation of glomerular leukocytes, and glomerular crescent formation). To evaluate histones as a therapeutic target, mice with established GN were treated with three different histone-neutralizing agents. Anti-histone IgG, recombinant activated protein C, and heparin were equally effective in abrogating severe GN, whereas combination therapy had no additive effects. Together, these results indicate that NET-related histone release during GN elicits cytotoxic and immunostimulatory effects. Furthermore, neutralizing extracellular histones is still therapeutic when initiated in established GN. Copyright © 2015 by the American Society of Nephrology.

DWI and complex brain network analysis predicts vascular cognitive impairment in spontaneous hypertensive rats undergoing executive function tests

Directory of Open Access Journals (Sweden)

Xavier eLópez-Gil

2014-07-01

Full Text Available The identification of biomarkers of vascular cognitive impairment is urgent for its early diagnosis. The aim of this study was to detect and monitor changes in brain structure and connectivity, and to correlate them with the decline in executive function. We examined the feasibility of early diagnostic magnetic resonance imaging to predict cognitive impairment before onset in an animal model of chronic hypertension: Spontaneously Hypertensive Rats. Cognitive performance was tested in an operant conditioning paradigm that evaluated learning, memory and behavioral flexibility skills. Behavioral tests were coupled with longitudinal diffusion weighted imaging acquired with 126 diffusion gradient directions and 0.3 mm3 isometric resolution at 10, 14, 18, 22, 26 and 40 weeks after birth. Diffusion weighted imaging was analyzed in 2 different ways, by regional characterization of diffusion tensor imaging indices, and by assessing changes in structural brain network organization based on Q-Ball tractography. Already at the first evaluated times, diffusion tensor imaging scalar maps revealed significant differences in many regions, suggesting loss of integrity in white and grey matter of spontaneously hypertensive rats when compared to normotensive control rats. In addition, graph theory analysis of the structural brain network demonstrated a significant decrease of hierarchical modularity, global and local efficacy, with predictive value as shown by regional 3-fold cross validation study. Moreover, these decreases were significantly correlated with the behavioral performance deficits observed at subsequent time points, suggesting that the diffusion weighted imaging and connectivity studies can unravel neuroimaging alterations even overt signs of cognitive impairment become apparent.

Hydro-mechanical foundation for blood swirling vortex flows formation in the cardio-vascular system and the problem of artificial heart creation

Directory of Open Access Journals (Sweden)

Sergey G. Chefranov

2013-11-01

Full Text Available Leonardo da Vinci perhaps was the first who paid attention to the energetic efficiency of existence of vortices emerging near sines of Valsalva and defining normal functioning (opening of aortal valve. However up to now a fundamental problem of defining of mechanisms of mysterious energetic efficiency of functioning of cardio-vascular system (CVS of blood feeding of the organism is still remaining significantly not solved and this is, for example, one of the main restriction for the creation of artificial heart and corresponding valve systems. In the present paper, results witnessing possible important role of the very hydro-mechanical mechanism in the realization of the noted energetic efficiency of CVS due to formation in the CVS of spiral structural organization of the arterial blood flow observed by methods of MRT and color Doppler-measuring in the left ventricular of the heart and in aorta.

The Biocarbon vascular access device (DiaTAB) for haemodialysis.

Science.gov (United States)

Smits, P J; Slooff, M J; Lichtendahl, D H; van der Hem, G K

1985-01-01

The Biocarbon vascular access device (DiaTAB) is a relatively new method in secondary access surgery. Punctures, often the cause of complications can be avoided because it is a no-needle method of dialysis. However thrombosis due to stenosis of the venous anastomosis or of the efferent vein is a continuing problem. A new experience is the fibrin flap formation under the plug of the device, which can be removed easily.

Uterine Vascular Lesions

Science.gov (United States)

Vijayakumar, Abhishek; Srinivas, Amruthashree; Chandrashekar, Babitha Moogali; Vijayakumar, Avinash

2013-01-01

Vascular lesions of the uterus are rare; most reported in the literature are arteriovenous malformations (AVMs). Uterine AVMs can be congenital or acquired. In recent years, there has been an increasing number of reports of acquired vascular lesions of the uterus following pregnancy, abortion, cesarean delivery, and curettage. It can be seen from these reports that there is confusion concerning the terminology of uterine vascular lesions. There is also a lack of diagnostic criteria and management guidelines, which has led to an increased number of unnecessary invasive procedures (eg, angiography, uterine artery embolization, hysterectomy for abnormal vaginal bleeding). This article familiarizes readers with various vascular lesions of the uterus and their management. PMID:24340126

Using NASA's GeneLab for VESGEN Systems Analysis of Vascular Phenotypes from Stress and Other Signaling Pathways

Science.gov (United States)

Parsons-Wingerter, P.; Weitzel, Alexander; Vyas, R. J.; Murray, M. C.; Vickerman, M. B.; Bhattacharya, S.; Wyatt, S. E.

2016-01-01

One fundamental requirement shared by humans with all higher terrestrial life forms, including other vertebrates, insects, and higher land plants, is a complex, fractally branching vascular system. NASA's VESsel GENeration Analysis (VESGEN) software maps and quantifies vascular trees, networks, and tree-network composites according to weighted physiological rules such as vessel connectivity, tapering and bifurcational branching. According to fluid dynamics, successful vascular transport requires a complex distributed system of highly regulated laminar flow. Microvascular branching rules within vertebrates, dicot leaves and the other organisms therefore display many similarities. A unifying perspective is that vascular patterning offers a useful readout of molecular signaling that necessarily integrates these complex pathways. VESGEN has elucidated changes in vascular pattern resulting from inflammatory, developmental and other signaling within numerous tissues and major model organisms studied for Space Biology. For a new VESGEN systems approach, we analyzed differential gene expression in leaves of Arabidopsis thaliana reported by GeneLab (GLDS-7) for spaceflight. Vascularrelated changes in leaf gene expression were identified that can potentially be phenocopied by mutants in ground-based experiments. To link transcriptional, protein and other molecular change with phenotype, alterations in the spatial and dynamic dimensions of vascular patterns for Arabidopsis leaves and other model species are being co-localized with signaling patterns of single molecular expression analyzed as information dimensions. Previously, Drosophila microarray data returned from space suggested significant changes in genes related to wing venation development that include EGF, Notch, Hedghog, Wingless and Dpp signaling. Phenotypes of increasingly abnormal ectopic wing venation in the (non-spaceflight) Drosophila wing generated by overexpression of a Notch antagonist were analyzed by

Fetal brain extracellular matrix boosts neuronal network formation in 3D bioengineered model of cortical brain tissue.

Science.gov (United States)

Sood, Disha; Chwalek, Karolina; Stuntz, Emily; Pouli, Dimitra; Du, Chuang; Tang-Schomer, Min; Georgakoudi, Irene; Black, Lauren D; Kaplan, David L

2016-01-01

The extracellular matrix (ECM) constituting up to 20% of the organ volume is a significant component of the brain due to its instructive role in the compartmentalization of functional microdomains in every brain structure. The composition, quantity and structure of ECM changes dramatically during the development of an organism greatly contributing to the remarkably sophisticated architecture and function of the brain. Since fetal brain is highly plastic, we hypothesize that the fetal brain ECM may contain cues promoting neural growth and differentiation, highly desired in regenerative medicine. Thus, we studied the effect of brain-derived fetal and adult ECM complemented with matricellular proteins on cortical neurons using in vitro 3D bioengineered model of cortical brain tissue. The tested parameters included neuronal network density, cell viability, calcium signaling and electrophysiology. Both, adult and fetal brain ECM as well as matricellular proteins significantly improved neural network formation as compared to single component, collagen I matrix. Additionally, the brain ECM improved cell viability and lowered glutamate release. The fetal brain ECM induced superior neural network formation, calcium signaling and spontaneous spiking activity over adult brain ECM. This study highlights the difference in the neuroinductive properties of fetal and adult brain ECM and suggests that delineating the basis for this divergence may have implications for regenerative medicine.

Fibulin-2 is present in murine vascular lesions and is important for smooth muscle cell migration

DEFF Research Database (Denmark)

Ström, A.; Olin, A. I.; Aspberg, A.

2006-01-01

/hyaluronan complexes, an ECM network that has been suggested to be important during tissue repair. In this study we have analysed the presence of fibulin-2 in two different models of murine vascular lesions. We have also examined how the fibulin-2/versican network influences SMC migration. Methods: Presence of fibulin......Objective: The vascular extracellular matrix (ECM) can affect smooth muscle cell (SMC) adhesion, migration and proliferation-events that are important during the atherosclerotic process. Fibulin-2 is a member of the ECM protein family of fibulins and has been found to cross-link versican...... and is upregulated during SMC phenotypic modulation in cell culture. Moreover, treatments with peptides that block the interaction between versican and fibulin-2 inhibit SMC migration in vitro. Conclusions: Fibulin-2 can be produced by SMC as a response to injury and may participate in the ECM organisation...

Hierarchical Fabrication of Engineered Vascularized Bone Biphasic Constructs via Dual 3D Bioprinting: Integrating Regional Bioactive Factors into Architectural Design.

Science.gov (United States)

Cui, Haitao; Zhu, Wei; Nowicki, Margaret; Zhou, Xuan; Khademhosseini, Ali; Zhang, Lijie Grace

2016-09-01

A biphasic artificial vascularized bone construct with regional bioactive factors is presented using dual 3D bioprinting platform technique, thereby forming a large functional bone grafts with organized vascular networks. Biocompatible mussel-inspired chemistry and "thiol-ene" click reaction are used to regionally immobilize bioactive factors during construct fabrication for modulating or improving cellular events. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

TCR triggering induces the formation of Lck-RACK1-actinin-1 multiprotein network affecting Lck redistribution

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Ondrej Ballek

2016-10-01

Full Text Available The initiation of T-cell signaling is critically dependent on the function of the member of Src family tyrosine kinases (SFKs, Lck. Upon TCR triggering, Lck kinase activity induces the nucleation of signal-transducing hubs that regulate the formation of complex signaling network and cytoskeletal rearrangement. In addition, the delivery of Lck function requires rapid and targeted membrane redistribution, but the mechanism underpinning this process is largely unknown. To gain insight into this process, we considered previously described proteins that could assist in this process via their capacity to interact with kinases and regulate their intracellular translocations. An adaptor protein, Receptor for Activated C Kinase 1 (RACK1, was chosen as a viable option and its capacity to bind Lck and aid the process of activation-induced redistribution of Lck was assessed. Our microscopic observation showed that T-cell activation induces a rapid, concomitant and transient co-redistribution of Lck and RACK1 into the forming immunological synapse. Consistent with this observation, the formation of transient RACK1-Lck complexes were detectable in primary CD4+ T-cells with their maximum levels peaking 10 seconds after TCR-CD4 co-aggregation. Moreover, RACK1 preferentially binds to a pool of kinase active pY394Lck which co-purifies with high molecular weight cellular fractions. The formation of RACK1-Lck complexes depends on functional SH2 and SH3 domains of Lck and includes several other signaling and cytoskeletal elements that transiently bind the complex. Notably, the F-actin-crosslinking protein, α-actinin-1, binds to RACK1 only in the presence of kinase active Lck suggesting that the formation of RACK1-pY394Lck-α-actinin-1 complex serves as a signal module coupling actin cytoskeleton bundling with productive TCR/CD4 triggering. In addition, the treatment of CD4+ T-cells with nocodazole, which disrupts the microtubular network, also blocked the formation

Framework for Explaining the Formation of Knowledge Intensive Entrepreneurial Born Global Firm: Entrepreneurial, Strategic and Network Based Constituents

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Vytaute Dlugoborskyte

2017-01-01

Full Text Available The nature of the knowledge based entrepreneurship relates to its essential reliance on research and development, deployment and maximization of research and development returns via technology development, and its commercialization via venturing. The paper aims to provide the empirically grounded framework for the analysis of the key determinants leading to the formation of R&D intensive entrepreneurial born global firm with a special focus on entrepreneurial firm and network theories. The unit of analysis chosen is the firm, while the focus is set on the firm behavior and strategic choices rather the business conditions per se. The paper aims to propose the definition of a born global firm as a specific form of entrepreneurial firm that forms while combining entrepreneurial, strategy and network constituents in a specific globally oriented constitution. Method of analysis applied is a multiple case study that was applied in order to build evidence on the interplay of strategy, networks and entrepreneurial constituents in the formation of knowledge intensive entrepreneurial born global firm. The small catching up country perspective adds on dynamics of the constituents as the framework and competitive conditions rapidly change in an uncertain direction.

SLM Produced Porous Titanium Implant Improvements for Enhanced Vascularization and Osteoblast Seeding

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Julia Matena

2015-04-01

Full Text Available To improve well-known titanium implants, pores can be used for increasing bone formation and close bone-implant interface. Selective Laser Melting (SLM enables the production of any geometry and was used for implant production with 250-µm pore size. The used pore size supports vessel ingrowth, as bone formation is strongly dependent on fast vascularization. Additionally, proangiogenic factors promote implant vascularization. To functionalize the titanium with proangiogenic factors, polycaprolactone (PCL coating can be used. The following proangiogenic factors were examined: vascular endothelial growth factor (VEGF, high mobility group box 1 (HMGB1 and chemokine (C-X-C motif ligand 12 (CXCL12. As different surfaces lead to different cell reactions, titanium and PCL coating were compared. The growing into the porous titanium structure of primary osteoblasts was examined by cross sections. Primary osteoblasts seeded on the different surfaces were compared using Live Cell Imaging (LCI. Cross sections showed cells had proliferated, but not migrated after seven days. Although the cell count was lower on titanium PCL implants in LCI, the cell count and cell spreading area development showed promising results for titanium PCL implants. HMGB1 showed the highest migration capacity for stimulating the endothelial cell line. Future perspective would be the incorporation of HMGB1 into PCL polymer for the realization of a slow factor release.

SLM Produced Porous Titanium Implant Improvements for Enhanced Vascularization and Osteoblast Seeding

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Matena, Julia; Petersen, Svea; Gieseke, Matthias; Kampmann, Andreas; Teske, Michael; Beyerbach, Martin; Murua Escobar, Hugo; Haferkamp, Heinz; Gellrich, Nils-Claudius; Nolte, Ingo

2015-01-01

To improve well-known titanium implants, pores can be used for increasing bone formation and close bone-implant interface. Selective Laser Melting (SLM) enables the production of any geometry and was used for implant production with 250-µm pore size. The used pore size supports vessel ingrowth, as bone formation is strongly dependent on fast vascularization. Additionally, proangiogenic factors promote implant vascularization. To functionalize the titanium with proangiogenic factors, polycaprolactone (PCL) coating can be used. The following proangiogenic factors were examined: vascular endothelial growth factor (VEGF), high mobility group box 1 (HMGB1) and chemokine (C-X-C motif) ligand 12 (CXCL12). As different surfaces lead to different cell reactions, titanium and PCL coating were compared. The growing into the porous titanium structure of primary osteoblasts was examined by cross sections. Primary osteoblasts seeded on the different surfaces were compared using Live Cell Imaging (LCI). Cross sections showed cells had proliferated, but not migrated after seven days. Although the cell count was lower on titanium PCL implants in LCI, the cell count and cell spreading area development showed promising results for titanium PCL implants. HMGB1 showed the highest migration capacity for stimulating the endothelial cell line. Future perspective would be the incorporation of HMGB1 into PCL polymer for the realization of a slow factor release. PMID:25849656

Influence of Androgen Receptor in Vascular Cells on Reperfusion following Hindlimb Ischaemia.

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Junxi Wu

Full Text Available Studies in global androgen receptor knockout (G-ARKO and orchidectomised mice suggest that androgen accelerates reperfusion of the ischaemic hindlimb by stimulating angiogenesis. This investigation used novel, vascular cell-specific ARKO mice to address the hypothesis that the impaired hindlimb reperfusion in G-ARKO mice was due to loss of AR from cells in the vascular wall.Mice with selective deletion of AR (ARKO from vascular smooth muscle cells (SM-ARKO, endothelial cells (VE-ARKO, or both (SM/VE-ARKO were compared with wild type (WT controls. Hindlimb ischaemia was induced in these mice by ligation and removal of the femoral artery. Post-operative reperfusion was reduced in SM-ARKO and SM/VE-ARKO mice. Immunohistochemistry indicated that this was accompanied by a reduced density of smooth muscle actin-positive vessels but no change in the density of isolectin B4-positive vessels in the gastrocnemius muscle. Deletion of AR from the endothelium (VE-ARKO did not alter post-operative reperfusion or vessel density. In an ex vivo (aortic ring culture model of angiogenesis, AR was not detected in vascular outgrowths and angiogenesis was not altered by vascular ARKO or by exposure to dihydrotestosterone (DHT 10-10-10-7M; 6 days.These results suggest that loss of AR from vascular smooth muscle, but not from the endothelium, contributes to impaired reperfusion in the ischaemic hindlimb of G-ARKO. Impaired reperfusion was associated with reduced collateral formation rather than reduced angiogenesis.

Estrogen, vascular estrogen receptor and hormone therapy in postmenopausal vascular disease.

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Khalil, Raouf A

2013-12-15

Cardiovascular disease (CVD) is less common in premenopausal women than men of the same age or postmenopausal women, suggesting vascular benefits of estrogen. Estrogen activates estrogen receptors ERα, ERβ and GPR30 in endothelium and vascular smooth muscle (VSM), which trigger downstream signaling pathways and lead to genomic and non-genomic vascular effects such as vasodilation, decreased VSM contraction and growth and reduced vascular remodeling. However, randomized clinical trials (RCTs), such as the Women's Health Initiative (WHI) and Heart and Estrogen/progestin Replacement Study (HERS), have shown little vascular benefits and even adverse events with menopausal hormone therapy (MHT), likely due to factors related to the MHT used, ER profile, and RCT design. Some MHT forms, dose, combinations or route of administration may have inadequate vascular effects. Age-related changes in ER amount, distribution, integrity and post-ER signaling could alter the vascular response to MHT. The subject's age, preexisting CVD, and hormone environment could also reduce the effects of MHT. Further evaluation of natural and synthetic estrogens, phytoestrogens, and selective estrogen-receptor modulators (SERMs), and the design of appropriate MHT combinations, dose, route and 'timing' could improve the effectiveness of conventional MHT and provide alternative therapies in the peri-menopausal period. Targeting ER using specific ER agonists, localized MHT delivery, and activation of specific post-ER signaling pathways could counter age-related changes in ER. Examination of the hormone environment and conditions associated with hormone imbalance such as polycystic ovary syndrome may reveal the causes of abnormal hormone-receptor interactions. Consideration of these factors in new RCTs such as the Kronos Early Estrogen Prevention Study (KEEPS) could enhance the vascular benefits of estrogen in postmenopausal CVD. Copyright © 2013 Elsevier Inc. All rights reserved.

The vascular surgery workforce: a survey of consultant vascular surgeons in the UK, 2014.

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Harkin, D W; Beard, J D; Shearman, C P; Wyatt, M G

2015-04-01

The purpose of this study was to describe the demographics, training, and practice characteristics of consultant vascular surgeons across the UK to provide an assessment of current, and inform future prediction of workforce needs. A questionnaire was developed using a modified Delphi process to generate questionnaire items. The questionnaire was emailed to all consultant vascular surgeons (n = 450) in the UK who were members of the Vascular Society of Great Britain & Ireland. 352 consultant vascular surgeons from 95 hospital trusts across the UK completed the survey (78% response rate). The mean age was 50.6 years old, the majority (62%) were mid-career, but 24% were above the age of 55. Currently, 92% are men and only 8% women. 93% work full-time, with 60% working >50 hours, and 21% working >60 hours per week. The average team was 5 to 6 (range 2-10) vascular surgeons, with 23% working in a large team of ≥8. 17% still work in small teams of ≤3. Over 90% of consultant vascular surgeons perform the major index vascular surgery procedures (aneurysm repair, carotid endarterectomy, infra-inguinal bypass, amputation). While 84% perform standard endovascular abdominal aortic aneurysm repair (EVAR), <50% perform more complex endovascular aortic therapy. The majority of vascular surgeons "like their job" (85%) and are "satisfied" (69%) with their job. 34% of consultant vascular surgeons indicated they were "extremely likely" to retire within the next 10 years. This study provides the first detailed analysis of the new specialty of vascular surgery as practiced in the UK. There is a need to plan for a significant expansion in the consultant vascular surgeon workforce in the UK over the next 10 years to maintain the status quo. Copyright © 2014 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Hydraulic efficiency and safety of vascular and non-vascular components in Pinus pinaster leaves.

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Charra-Vaskou, Katline; Badel, Eric; Burlett, Régis; Cochard, Hervé; Delzon, Sylvain; Mayr, Stefan

2012-09-01

Leaves, the distal section of the soil-plant-atmosphere continuum, exhibit the lowest water potentials in a plant. In contrast to angiosperm leaves, knowledge of the hydraulic architecture of conifer needles is scant. We investigated the hydraulic efficiency and safety of Pinus pinaster needles, comparing different techniques. The xylem hydraulic conductivity (k(s)) and embolism vulnerability (P(50)) of both needle and stem were measured using the cavitron technique. The conductance and vulnerability of whole needles were measured via rehydration kinetics, and Cryo-SEM and 3D X-ray microtomographic observations were used as reference tools to validate physical measurements. The needle xylem of P. pinaster had lower hydraulic efficiency (k(s) = 2.0 × 10(-4) m(2) MPa(-1) s(-1)) and safety (P(50) = - 1.5 MPa) than stem xylem (k(s) = 7.7 × 10(-4) m(2) MPa(-1) s(-1); P(50) = - 3.6 to - 3.2 MPa). P(50) of whole needles (both extra-vascular and vascular pathways) was - 0.5 MPa, suggesting that non-vascular tissues were more vulnerable than the xylem. During dehydration to - 3.5 MPa, collapse and embolism in xylem tracheids, and gap formation in surrounding tissues were observed. However, a discrepancy in hydraulic and acoustic results appeared compared with visualizations, arguing for greater caution with these techniques when applied to needles. Our results indicate that the most distal parts of the water transport pathway are limiting for hydraulics of P. pinaster. Needle tissues exhibit a low hydraulic efficiency and low hydraulic safety, but may also act to buffer short-term water deficits, thus preventing xylem embolism.

VEGFR tyrosine kinase inhibitor II (VRI) induced vascular insufficiency in zebrafish as a model for studying vascular toxicity and vascular preservation

International Nuclear Information System (INIS)

Li, Shang; Dang, Yuan Ye; Oi Lam Che, Ginny; Kwan, Yiu Wa; Chan, Shun Wan; Leung, George Pak Heng; Lee, Simon Ming Yuen; Hoi, Maggie Pui Man

2014-01-01

In ischemic disorders such as chronic wounds and myocardial ischemia, there is inadequate tissue perfusion due to vascular insufficiency. Besides, it has been observed that prolonged use of anti-angiogenic agents in cancer therapy produces cardiovascular toxicity caused by impaired vessel integrity and regeneration. In the present study, we used VEGFR tyrosine kinase inhibitor II (VRI) to chemically induce vascular insufficiency in zebrafish in vivo and human umbilical vein endothelial cells (HUVEC) in vitro to further study the mechanisms of vascular morphogenesis in these pathological conditions. We also explored the possibility of treating vascular insufficiency by enhancing vascular regeneration and repair with pharmacological intervention. We observed that pretreatment of VRI induced blood vessel loss in developing zebrafish by inhibiting angiogenesis and increasing endothelial cell apoptosis, accompanied by down-regulation of kdr, kdrl and flt-1 genes expression. The VRI-induced blood vessel loss in zebrafish could be restored by post-treatment of calycosin, a cardiovascular protective isoflavone. Similarly, VRI induced cytotoxicity and apoptosis in HUVEC which could be rescued by calycosin post-treatment. Further investigation of the underlying mechanisms showed that the PI3K/AKT/Bad cell survival pathway was a main contributor of the vascular regenerative effect of calycosin. These findings indicated that the cardiovascular toxicity in anti-angiogenic therapy was mainly caused by insufficient endothelial cell survival, suggesting its essential role in vascular integrity, repair and regeneration. In addition, we showed that VRI-induced blood vessel loss in zebrafish represented a simple and effective in vivo model for studying vascular insufficiency and evaluating cancer drug vascular toxicities. - Highlights: • In vivo VRI model • Rescue effects of calycosin • Calycosin EC survival pathways

Estrogen-induced DNA synthesis in vascular endothelial cells is mediated by ROS signaling

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Felty Quentin

2006-04-01

Full Text Available Abstract Background Since estrogen is known to increase vascular endothelial cell growth, elevated estrogen exposure from hormone replacement therapy or oral contraceptives has the potential to contribute in the development of abnormal proliferative vascular lesions and subsequent thickening of the vasculature. How estrogen may support or promote vascular lesions is not clear. We have examined in this study whether estrogen exposure to vascular endothelial cells increase the formation of reactive oxygen species (ROS, and estrogen-induced ROS is involved in the growth of endothelial cells. Methods The effect of estrogen on the production of intracellular oxidants and the role of estrogen-induced ROS on cell growth was studied in human umbilical vein endothelial cells. ROS were measured by monitoring the oxidation of 2'7'-dichlorofluorescin by spectrofluorometry. Endothelial cell growth was measured by a colorimetric immunoassay based on BrdU incorporation into DNA. Results Physiological concentrations of estrogen (367 fmol and 3.67 pmol triggered a rapid 2-fold increase in intracellular oxidants in endothelial cells. E2-induced ROS formation was inhibited to basal levels by cotreatment with the mitochondrial inhibitor rotenone (2 μM and xanthine oxidase inhibitor allopurinol (50 μM. Inhibitors of NAD(PH oxidase, apocynin and DPI, did not block E2-induced ROS formation. Furthermore, the NOS inhibitor, L-NAME, did not prevent the increase in E2-induced ROS. These findings indicate both mitochondria and xanthine oxidase are the source of ROS in estrogen treated vascular endothelial cells. E2 treated cells showed a 2-fold induction of BrdU incorporation at 18 h which was not observed in cells exposed to vehicle alone. Cotreatment with ebselen (20 μM and NAC (1 mM inhibited E2-induced BrdU incorporation without affecting the basal levels of DNA synthesis. The observed inhibitory effect of NAC and ebselen on E2-induced DNA synthesis was also shown

Frequency Resource Sharing and Allocation Scheme Based on Coalition Formation Game in Hybrid D2D-Cellular Network

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Qing Ou

2015-01-01

Full Text Available A distributed cooperation scheme on frequency resource sharing is proposed to improve the quality of service (QoS in device-to-device (D2D communications underlaying cellular networks. Specifically, we formulate the resource allocation problem as a coalition formation game with transferable utility, in which all users have the incentive to cooperate with some others and form a competitive group to maximize the probability of obtaining their favorite spectrum resources. Taking the cost for coalition formation into account, such as the path loss for data sharing, we prove that the core of the proposed game is empty, which shows the impossibility of grand coalition. Hence, we propose a distributed merge-and-split based coalition formation algorithm based on a new defined Max-Coalition order to effectively solve the coalition game. Compared with the exhaustive search, our algorithm has much lower computer complexity. In addition, we prove that stability and convergence of the proposed algorithm using the concept of a defection function. Finally, the simulation results show that the proposed scheme achieves a suboptimal performance in terms of network sum rate compared with the centralized optimal resource allocation scheme obtained via exhaustive search.

GHSR deficiency suppresses neointimal formation in injured mouse arteries

International Nuclear Information System (INIS)

Li, Jing; Zhang, Man; Wang, Mo; Wang, Zhipeng; Liu, Yahan; Zhang, Weizhen; Wang, Nanping

2016-01-01

Growth hormone secretagogue receptor (GHSR) is involved in appetite regulation and energy homeostasis. In the present study, we examined the role of GHSR in neointimal formation following vascular injury. In the mouse model of femoral artery wire injury, we found that vessel intima-to-media ratio was significantly reduced in GHSR deficiency (GHSR −/− ) mice compared with that in wild-type mice. Immunohistochemical staining showed that the smooth muscle cell (SMCs) in the neointima were significantly decreased in the injured arteries of GHSR −/− mice which was associated with decreased SMC proliferation and migration. Furthermore, immunoblotting demonstrated that, in cultured rat aortic SMCs, small interfering RNA-mediated GHSR knockdown suppressed the activation of Akt and ERK1/2 signaling pathway. These findings suggested a novel role of GHSR in neointimal formation likely via promoting the proliferation and migration of SMCs involving Akt and ERK1/2 signaling. Therefore, GHSR may be a potential therapeutic target in restenosis and vascular remodeling. - Highlights: • GHSR deficiency inhibits neointimal formation after vascular injury. • GHSR deficiency suppresses SMCs numbers in vivo. • Knockdown GHSR represses SMCs proliferation and migration in vitro. • Knockdown GHSR inhibited Akt and ERK1/2 phosphorylation in SMCs.

Drug use Discrimination Predicts Formation of High-Risk Social Networks: Examining Social Pathways of Discrimination.

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Crawford, Natalie D; Ford, Chandra; Rudolph, Abby; Kim, BoRin; Lewis, Crystal M

2017-09-01

Experiences of discrimination, or social marginalization and ostracism, may lead to the formation of social networks characterized by inequality. For example, those who experience discrimination may be more likely to develop drug use and sexual partnerships with others who are at increased risk for HIV compared to those without experiences of discrimination. This is critical as engaging in risk behaviors with others who are more likely to be HIV positive can increase one's risk of HIV. We used log-binomial regression models to examine the relationship between drug use, racial and incarceration discrimination with changes in the composition of one's risk network among 502 persons who use drugs. We examined both absolute and proportional changes with respect to sex partners, drug use partners, and injecting partners, after accounting for individual risk behaviors. At baseline, participants were predominately male (70%), black or Latino (91%), un-married (85%), and used crack (64%). Among those followed-up (67%), having experienced discrimination due to drug use was significantly related to increases in the absolute number of sex networks and drug networks over time. No types of discrimination were related to changes in the proportion of high-risk network members. Discrimination may increase one's risk of HIV acquisition by leading them to preferentially form risk relationships with higher-risk individuals, thereby perpetuating racial and ethnic inequities in HIV. Future social network studies and behavioral interventions should consider whether social discrimination plays a role in HIV transmission.

The Quantitative Measurements of Vascular Density and Flow Areas of Macula Using Optical Coherence Tomography Angiography in Normal Volunteers.

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Ghassemi, Fariba; Fadakar, Kaveh; Bazvand, Fatemeh; Mirshahi, Reza; Mohebbi, Masoumeh; Sabour, Siamak

2017-06-01

The quantification of the density of macular vascular networks and blood flow areas in the foveal and parafoveal area in healthy subjects using optical coherence tomography angiography (OCTA). Cross-sectional, prospective study in an institutional setting at the Retina Services of Farabi Eye Hospital. One hundred twelve normal volunteers with no known ocular or systemic disease were included, including patient numbers (one or both eyes), selection procedures, inclusion/exclusion criteria, randomization procedure, and masking. En face angiogram OCTA was performed on a 3 mm × 3 mm region centered on the macula. Automated thresholding and measuring algorithm method for foveal and parafoveal blood flow and vascular density (VD) were used. The density of macular vascular networks and blood flow area in the foveal and parafoveal area were measured. A total of 224 healthy eyes from 112 subjects with a mean age of 36.4 years ± 11.3 years were included. In the foveal region, the VD of the superficial capillary network (sCN) was significantly higher than that of the deep capillary network (dCN) (31.1% ± 5.5% vs. 28.3% ± 7.2%; P < .001), whereas in the parafoveal area, VD was higher in the dCN (62.24% ± 2.8% vs. 56.5% ± 2.5%; P < .001). Flow area in the 1-mm radius circle in the sCN was less than in the dCN. Superficial foveal avascular zone (sFAZ) size was negatively correlated with the VD of the foveal sCN, but in the deep FAZ (dFAZ) was not correlated with VD or blood flow area of the fovea. There was no difference between measured VD and blood flow surface area in both eyes of the subjects. OCTA could be used as a noninvasive, repeatable, layer-free method in quantitative evaluation of VD and blood flow of macular area. The normal quantities of the vascular plexus density and flow will help in better understanding the pathophysiological basis of the vascular disease of retina. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:478-486.]. Copyright 2017, SLACK

Vildagliptin Stimulates Endothelial Cell Network Formation and Ischemia-induced Revascularization via an Endothelial Nitric-oxide Synthase-dependent Mechanism*

Science.gov (United States)

Ishii, Masakazu; Shibata, Rei; Kondo, Kazuhisa; Kambara, Takahiro; Shimizu, Yuuki; Tanigawa, Tohru; Bando, Yasuko K.; Nishimura, Masahiro; Ouchi, Noriyuki; Murohara, Toyoaki

2014-01-01

Dipeptidyl peptidase-4 inhibitors are known to lower glucose levels and are also beneficial in the management of cardiovascular disease. Here, we investigated whether a dipeptidyl peptidase-4 inhibitor, vildagliptin, modulates endothelial cell network formation and revascularization processes in vitro and in vivo. Treatment with vildagliptin enhanced blood flow recovery and capillary density in the ischemic limbs of wild-type mice, with accompanying increases in phosphorylation of Akt and endothelial nitric-oxide synthase (eNOS). In contrast to wild-type mice, treatment with vildagliptin did not improve blood flow in ischemic muscles of eNOS-deficient mice. Treatment with vildagliptin increased the levels of glucagon-like peptide-1 (GLP-1) and adiponectin, which have protective effects on the vasculature. Both vildagliptin and GLP-1 increased the differentiation of cultured human umbilical vein endothelial cells (HUVECs) into vascular-like structures, although vildagliptin was less effective than GLP-1. GLP-1 and vildagliptin also stimulated the phosphorylation of Akt and eNOS in HUVECs. Pretreatment with a PI3 kinase or NOS inhibitor blocked the stimulatory effects of both vildagliptin and GLP-1 on HUVEC differentiation. Furthermore, treatment with vildagliptin only partially increased the limb flow of ischemic muscle in adiponectin-deficient mice in vivo. GLP-1, but not vildagliptin, significantly increased adiponectin expression in differentiated 3T3-L1 adipocytes in vitro. These data indicate that vildagliptin promotes endothelial cell function via eNOS signaling, an effect that may be mediated by both GLP-1-dependent and GLP-1-independent mechanisms. The beneficial activity of GLP-1 for revascularization may also be partially mediated by its ability to increase adiponectin production. PMID:25100725

Biological transportation networks: Modeling and simulation

KAUST Repository

Albi, Giacomo

2015-09-15

We present a model for biological network formation originally introduced by Cai and Hu [Adaptation and optimization of biological transport networks, Phys. Rev. Lett. 111 (2013) 138701]. The modeling of fluid transportation (e.g., leaf venation and angiogenesis) and ion transportation networks (e.g., neural networks) is explained in detail and basic analytical features like the gradient flow structure of the fluid transportation network model and the impact of the model parameters on the geometry and topology of network formation are analyzed. We also present a numerical finite-element based discretization scheme and discuss sample cases of network formation simulations.

Tofacitinib Ameliorates Murine Lupus and Its Associated Vascular Dysfunction.

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Furumoto, Yasuko; Smith, Carolyne K; Blanco, Luz; Zhao, Wenpu; Brooks, Stephen R; Thacker, Seth G; Abdalrahman, Zarzour; Sciumè, Giuseppe; Tsai, Wanxia L; Trier, Anna M; Nunez, Leti; Mast, Laurel; Hoffmann, Victoria; Remaley, Alan T; O'Shea, John J; Kaplan, Mariana J; Gadina, Massimo

2017-01-01

Dysregulation of innate and adaptive immune responses contributes to the pathogenesis of systemic lupus erythematosus (SLE) and its associated premature vascular damage. No drug to date targets both systemic inflammatory disease and the cardiovascular complications of SLE. Tofacitinib is a JAK inhibitor that blocks signaling downstream of multiple cytokines implicated in lupus pathogenesis. While clinical trials have shown that tofacitinib exhibits significant clinical efficacy in various autoimmune diseases, its role in SLE and the associated vascular pathology remains to be characterized. MRL/lpr lupus-prone mice were administered tofacitinib or vehicle by gavage for 6 weeks (therapeutic arm) or 8 weeks (preventive arm). Nephritis, skin inflammation, serum levels of autoantibodies and cytokines, mononuclear cell phenotype and gene expression, neutrophil extracellular traps (NETs) release, endothelium-dependent vasorelaxation, and endothelial differentiation were compared in treated and untreated mice. Treatment with tofacitinib led to significant improvement in measures of disease activity, including nephritis, skin inflammation, and autoantibody production. In addition, tofacitinib treatment reduced serum levels of proinflammatory cytokines and interferon responses in splenocytes and kidney tissue. Tofacitinib also modulated the formation of NETs and significantly increased endothelium-dependent vasorelaxation and endothelial differentiation. The drug was effective in both preventive and therapeutic strategies. Tofacitinib modulates the innate and adaptive immune responses, ameliorates murine lupus, and improves vascular function. These results indicate that JAK inhibitors have the potential to be beneficial in SLE and its associated vascular damage. © 2016, American College of Rheumatology.

The behavior of the vascular system in the experimental tumor radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Yamaura, H; Matsuzawa, T; Sato, H [Tohoku Univ., Sendai (Japan). Research Inst. for Tuberculosis, Leprosy and Cancer; Ito, Yasuhiko

1975-07-01

The rat ascites hepatoma AH109A transplanted and grown in the rat transparent chamber developed a tumor specific vascular system, the process of which was quantitatively studied because of the vascular length, surface area, and volume per mm/sup 3/ of tissue. The values changed characteristically in each stage of the course. The tumor was irradiated in a chamber with 3000 R of /sup 60/Co ..gamma..-rays, and the tumor cells died leaving behind highly dense capillary networks, which gradually returned to normal level by 7 days after irradiation. The blood vessels, either preformed or newly formed, in the control tissue without tumor were not damaged by this dose. But the proliferation of capillary buds were inhibited slightly with 400 R and completely with 4000 R.

Rapid prototyping of biomimetic vascular phantoms for hyperspectral reflectance imaging

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Ghassemi, Pejhman; Wang, Jianting; Melchiorri, Anthony J.; Ramella-Roman, Jessica C.; Mathews, Scott A.; Coburn, James C.; Sorg, Brian S.; Chen, Yu; Joshua Pfefer, T.

2015-12-01

The emerging technique of rapid prototyping with three-dimensional (3-D) printers provides a simple yet revolutionary method for fabricating objects with arbitrary geometry. The use of 3-D printing for generating morphologically biomimetic tissue phantoms based on medical images represents a potentially major advance over existing phantom approaches. Toward the goal of image-defined phantoms, we converted a segmented fundus image of the human retina into a matrix format and edited it to achieve a geometry suitable for printing. Phantoms with vessel-simulating channels were then printed using a photoreactive resin providing biologically relevant turbidity, as determined by spectrophotometry. The morphology of printed vessels was validated by x-ray microcomputed tomography. Channels were filled with hemoglobin (Hb) solutions undergoing desaturation, and phantoms were imaged with a near-infrared hyperspectral reflectance imaging system. Additionally, a phantom was printed incorporating two disjoint vascular networks at different depths, each filled with Hb solutions at different saturation levels. Light propagation effects noted during these measurements-including the influence of vessel density and depth on Hb concentration and saturation estimates, and the effect of wavelength on vessel visualization depth-were evaluated. Overall, our findings indicated that 3-D-printed biomimetic phantoms hold significant potential as realistic and practical tools for elucidating light-tissue interactions and characterizing biophotonic system performance.

Histology atlas of the developing mouse hepatobiliary hemolymphatic vascular system with emphasis on embryonic days 11.5-18.5 and early postnatal development

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A critical event in fetal development is the proper formation of the vascular system, of which the hepatobiliary system plays a pivotal role. This has lead pathologists and scientists to utilize transgenic mice to identify developmental disorders associated with the hepatobiliary vascular system. Va...

Flow distributions and spatial correlations in human brain capillary networks

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Lorthois, Sylvie; Peyrounette, Myriam; Larue, Anne; Le Borgne, Tanguy

2015-11-01

The vascular system of the human brain cortex is composed of a space filling mesh-like capillary network connected upstream and downstream to branched quasi-fractal arterioles and venules. The distribution of blood flow rates in these networks may affect the efficiency of oxygen transfer processes. Here, we investigate the distribution and correlation properties of blood flow velocities from numerical simulations in large 3D human intra-cortical vascular network (10000 segments) obtained from an anatomical database. In each segment, flow is solved from a 1D non-linear model taking account of the complex rheological properties of blood flow in microcirculation to deduce blood pressure, blood flow and red blood cell volume fraction distributions throughout the network. The network structural complexity is found to impart broad and spatially correlated Lagrangian velocity distributions, leading to power law transit time distributions. The origins of this behavior (existence of velocity correlations in capillary networks, influence of the coupling with the feeding arterioles and draining veins, topological disorder, complex blood rheology) are studied by comparison with results obtained in various model capillary networks of controlled disorder. ERC BrainMicroFlow GA615102, ERC ReactiveFronts GA648377.

Microarray Data Analysis of Space Grown Arabidopsis Leaves for Genes Important in Vascular Patterning

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Weitzeal, A. J.; Wyatt, S. E.; Parsons-Wingerter, P.

2016-01-01

Venation patterning in leaves is a major determinant of photosynthesis efficiency because of its dependency on vascular transport of photoassimilates, water, and minerals. Arabidopsis thaliana grown in microgravity show delayed growth and leaf maturation. Gene expression data from the roots, hypocotyl, and leaves of A. thaliana grown during spaceflight vs. ground control analyzed by Affymetrix microarray are available through NASAs GeneLab (GLDS-7). We analyzed the data for differential expression of genes in leaves resulting from the effects of spaceflight on vascular patterning. Two genes were found by preliminary analysis to be upregulated during spaceflight that may be related to vascular formation. The genes are responsible for coding an ARGOS like protein (potentially affecting cell elongation in the leaves), and an F-boxkelch-repeat protein (possibly contributing to protoxylem specification). Further analysis that will focus on raw data quality assessment and a moderated t-test may further confirm upregulation of the two genes and/or identify other gene candidates. Plants defective in these genes will then be assessed for phenotype by the mapping and quantification of leaf vascular patterning by NASAs VESsel GENeration (VESGEN) software to model specific vascular differences of plants grown in spaceflight.

Surgical treatment of complications associated with the Angio-Seal vascular closure device.

Science.gov (United States)

Cikirikcioglu, Mustafa; Cherian, Sanjay; Keil, Vera; Manzano, Norman; Gemayel, Gino; Theologou, Thomas; Kalangos, Afksendiyos

2011-05-01

Vascular closure devices are used to provide quick hemostasis and early ambulation after percutaneous interventions. The Angio-Seal (AS) vascular closure device forms a mechanical seal by closing the puncture site located between a bioabsorbable anchor within the lumen and a collagen sponge on the adventitia. Although morbidities associated with AS are reportedly infrequent, even the slightest inaccuracy in device implantation may result in displacement of these device components, leading to sudden and severe complications. We report the surgical treatment of complications associated with the use of AS in four patients, including acute limb ischemia, pseudoaneurysm formation, significant hemorrhage, and hypovolemic shock. A common factor in all these cases was that the components of the AS device were displaced from their original site of implantation, stressing the importance of proper device placement. All patients underwent successful surgical vascular repair. Our report highlights the need for exercising extreme care during device implantation, and also the requirement for vigilant inspection for any associated vascular complications commencing immediately after device implantation. It is vital that these device components are actively looked for and removed during surgical exploration so as to prevent future complications. Copyright © 2011. Published by Elsevier Inc.

Multi-focus Image Fusion Using Epifluorescence Microscopy for Robust Vascular Segmentation

OpenAIRE

Pelapur, Rengarajan; Prasath, Surya; Palaniappan, Kannappan

2014-01-01

We are building a computerized image analysis system for Dura Mater vascular network from fluorescence microscopy images. We propose a system that couples a multi-focus image fusion module with a robust adaptive filtering based segmentation. The robust adaptive filtering scheme handles noise without destroying small structures, and the multi focal image fusion considerably improves the overall segmentation quality by integrating information from multiple images. Based on the segmenta...

The challenge of establishing treatment efficacy for cutaneous vascular manifestations of systemic sclerosis.

Science.gov (United States)

Pauling, John D

2018-05-01

The cutaneous vascular manifestations of systemic sclerosis (SSc) comprise Raynaud's phenomenon, cutaneous ulceration, telangiectasia formation and critical digital ischaemia; each of which are associated with significant disease-related morbidity. Despite the availability of multiple classes of vasodilator therapy, many of which have been the subject of RCTs, a limited number of pharmacological interventions are currently approved for the management of cutaneous vascular manifestations of SSc. Areas covered: A major challenge has been demonstrating treatment efficacy with examples of promising therapies yielding contrasting results in controlled trial settings. Differences between consensus best-practice guidelines, evidence-based recommendations and marketing approvals in different jurisdictions has resulted in geographic variation in clinical practice concerning the management of cutaneous vascular manifestations of SSc. Difficulty demonstrating treatment efficacy risks waning industry engagement for drug development programmes in this field. This article highlights the key challenges in establishing treatment efficacy and barriers that must be overcome to support successful clinical trial programmes across the spectrum of cutaneous vascular manifestations of SSc. Expert commentary: The paucity of approved treatments for cutaneous vascular manifestations of SSc relates as much to challenges in clinical trial design and the need for reliable clinical trial endpoints, as to lack of therapeutic options.

Connections matter: channeled hydrogels to improve vascularization

Directory of Open Access Journals (Sweden)

Severin eMuehleder

2014-11-01

Full Text Available The use of cell-laden hydrogels to engineer soft tissue has been emerging within the past years. Despite several newly developed and sophisticated techniques to encapsulate different cell types the importance of vascularization of the engineered constructs is often underestimated. As a result, cell death within a construct leads to impaired function and inclusion of the implant. Here, we discuss the fabrication of hollow channels within hydrogels as a promising strategy to facilitate vascularization. Furthermore, we present an overview on the feasible use of removable spacers, 3D laser- and planar processing strategies to create channels within hydrogels. The implementation of these structures promotes control over cell distribution and increases oxygen transport and nutrient supply in vitro. However, many studies lack the use of endothelial cells in their approaches leaving out an important factor to enhance vessel ingrowth and anastomosis formation upon implantation. In addition, the adequate endothelial cell type needs to be considered to make these approaches bridge the gap to in vivo applications.

The in vivo blood compatibility of bio-inspired small diameter vascular graft: effect of submicron longitudinally aligned topography

Science.gov (United States)

2013-01-01

Background Cardiovascular disease is the leading cause of deaths worldwide and the arterial reconstructive surgery remains the treatment of choice. Although large diameter vascular grafts have been widely used in clinical practices, there is an urgent need to develop a small diameter vascular graft with enhanced blood compatibility. Herein, we fabricated a small diameter vascular graft with submicron longitudinally aligned topography, which mimicked the tunica intima of the native arterial vessels and were tested in Sprague–Dawley (SD) rats. Methods Vascular grafts with aligned and smooth topography were prepared by electrospinning and were connected to the abdominal aorta of the SD rats to evaluate their blood compatibility. Graft patency and platelet adhesion were evaluated by color Doppler ultrasound and immunofluorescence respectively. Results We observed a significant higher patency rate (p = 0.021) and less thrombus formation in vascular graft with aligned topography than vascular graft with smooth topography. However, no significant difference between the adhesion rates on both vascular grafts (smooth/aligned: 0.35‰/0.12‰, p > 0.05) was observed. Moreover, both vascular grafts had few adherent activated platelets on the luminal surface. Conclusion Bionic vascular graft showed enhanced blood compatibility due to the effect of surface topography. Therefore, it has considerable potential for using in clinical application. PMID:24083888

Heterotopic bone formation in the musculus latissimus dorsi of sheep using β-tricalcium phosphate scaffolds: evaluation of an extended prefabrication time on bone formation and matrix degeneration.

Science.gov (United States)

Spalthoff, S; Jehn, P; Zimmerer, R; Möllmann, U; Gellrich, N-C; Kokemueller, H

2015-06-01

We previously generated viable heterotopic bone in living animals and found that 3 months of intrinsic vascularization improved bone formation and matrix degeneration. In this study, we varied the pre-vascularization time to determine its effects on the kinetics of bone formation and ceramic degradation. Two 25-mm-long cylindrical β-tricalcium phosphate scaffolds were filled intraoperatively with autogenous iliac crest bone marrow and implanted in the latissimus dorsi muscle in six sheep. To examine the effect of axial perfusion, one scaffold was surgically implanted with (group C) or without (group D) a central vascular bundle. All animals were sacrificed 6 months postoperatively and histomorphometric measurements were compared to previous results. All implanted scaffolds exhibited ectopic bone growth. However, bone growth was not significantly different between the 3-month (group A, 0.191±0.097 vs. group C, 0.237±0.075; P=0.345) and 6-month (group B, 0.303±0.105 vs. group D, 0.365±0.258; P=0.549) pre-vascularization durations, regardless of vessel supply; early differences between surgically and extrinsically vascularized constructs disappeared after 6 months. Here, we describe a reliable procedure for generating ectopic bone in vivo. A 3-month pre-vascularization duration appears sufficient and ceramic degradation proceeds in accordance with bone generation, supporting the hypothesis of cell-mediated resorption. Copyright © 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Popliteal vascular entrapment syndrome caused by a rare anomalous slip of the lateral head of the gastrocnemius muscle

International Nuclear Information System (INIS)

Liu, Patrick T.; Moyer, Adrian C.; Huettl, Eric A.; Fowl, Richard J.; Stone, William M.

2005-01-01

Popliteal vascular entrapment syndrome can result in calf claudication, aneurysm formation, distal arterial emboli, or popliteal vessel thrombosis. The most commonly reported causes of this syndrome have been anomalies of the medial head of the gastrocnemius muscle as it relates to the course of the popliteal artery. We report two cases of rare anomalous slips of the lateral head of the gastrocnemius muscle causing popliteal vascular entrapment syndrome. (orig.)

Vascular grading of angiogenesis

DEFF Research Database (Denmark)

Hansen, S; Grabau, D A; Sørensen, Flemming Brandt

2000-01-01

The study aimed to evaluate the prognostic value of angiogenesis by vascular grading of primary breast tumours, and to evaluate the prognostic impact of adding the vascular grade to the Nottingham Prognostic Index (NPI). The investigation included 836 patients. The median follow-up time was 11...... years and 4 months. The microvessels were immunohistochemically stained by antibodies against CD34. Angiogenesis was graded semiquantitatively by subjective scoring into three groups according to the expected number of microvessels in the most vascular tumour area. The vascular grading between observers...... for 24% of the patients, who had a shift in prognostic group, as compared to NPI, and implied a better prognostic dissemination. We concluded that the angiogenesis determined by vascular grading has independent prognostic value of clinical relevance for patients with breast cancer....

Vascular grading of angiogenesis

DEFF Research Database (Denmark)

Hansen, S; Grabau, D A; Sørensen, Flemming Brandt

2000-01-01

The study aimed to evaluate the prognostic value of angiogenesis by vascular grading of primary breast tumours, and to evaluate the prognostic impact of adding the vascular grade to the Nottingham Prognostic Index (NPI). The investigation included 836 patients. The median follow-up time was 11...... years and 4 months. The microvessels were immunohistochemically stained by antibodies against CD34. Angiogenesis was graded semiquantitatively by subjective scoring into three groups according to the expected number of microvessels in the most vascular tumour area. The vascular grading between observers...... impact for 24% of the patients, who had a shift in prognostic group, as compared to NPI, and implied a better prognostic dissemination. We concluded that the angiogenesis determined by vascular grading has independent prognostic value of clinical relevance for patients with breast cancer....

Effects of Hofmeister salt series on gluten network formation: Part I. Cation series.

Science.gov (United States)

Tuhumury, H C D; Small, D M; Day, L

2016-12-01

Different cationic salts were used to investigate the effects of the Hofmeister salt series on gluten network formation. The effects of cationic salts on wheat flour dough mixing properties, the rheological and the chemical properties of the gluten extracted from the dough with different respective salts, were investigated. The specific influence of different cationic salts on the gluten structure formation during dough mixing, compared to the sodium ion, were determined. The effects of different cations on dough and gluten of different flours mostly followed the Hofmeister series (NH4(+), K(+), Na(+), Mg(2+) and Ca(2+)). The impacts of cations on gluten structure and dough rheology at levels tested were relatively small. Therefore, the replacement of sodium from a technological standpoint is possible, particularly by monovalent cations such as NH4(+), or K(+). However the levels of replacement need to take into account sensory attributes of the cationic salts. Copyright © 2016 Elsevier Ltd. All rights reserved.

Generating functional analysis of complex formation and dissociation in large protein interaction networks

International Nuclear Information System (INIS)

Coolen, A C C; Rabello, S

2009-01-01

We analyze large systems of interacting proteins, using techniques from the non-equilibrium statistical mechanics of disordered many-particle systems. Apart from protein production and removal, the most relevant microscopic processes in the proteome are complex formation and dissociation, and the microscopic degrees of freedom are the evolving concentrations of unbound proteins (in multiple post-translational states) and of protein complexes. Here we only include dimer-complexes, for mathematical simplicity, and we draw the network that describes which proteins are reaction partners from an ensemble of random graphs with an arbitrary degree distribution. We show how generating functional analysis methods can be used successfully to derive closed equations for dynamical order parameters, representing an exact macroscopic description of the complex formation and dissociation dynamics in the infinite system limit. We end this paper with a discussion of the possible routes towards solving the nontrivial order parameter equations, either exactly (in specific limits) or approximately.

Pathophysiology of the vascular wall and its relevance for cerebrovascular disorders in aged rodents.

Science.gov (United States)

Popa-Wagner, A; Pirici, D; Petcu, E B; Mogoanta, L; Buga, A-M; Rosen, C L; Leon, R; Huber, J

2010-08-01

Chronic hypertension and cerebral amyloid angiopathy (CAA) are the main pathologies which can induce the rupture of cerebral vessels and intracerebral hemorrhages, as a result of degenerative changes in the vascular wall. A lot of progress has been made in this direction since the successful creation of the first mouse model for the study of Alzheimer's disease (AD), as the spectrum of AD pathology includes a plethora of changes found in pure cerebrovascular diseases. We describe here some of these mouse models having important vascular changes that parallel human AD pathology, and more importantly, we show how these models have helped us understand more about the mechanisms that lead to CAA formation. An important cellular event associated with reduced structural and functional recovery after stroke in aged animals is the early formation of a scar in the infarcted region that impairs subsequent neural recovery and repair. We review recent evidence showing that the rapid formation of the glial scar following stroke in aged rats is associated with premature cellular proliferation that originates primarily from the walls of capillaries in the corpus callosum adjacent to the infarcted region. After stroke several vascular mechanisms are turned-on immediately to protect the brain from further damage and help subsequent neuroregeneration and functional recovery. Although does occur after stroke, vasculogenesis is overshadowed in its protective/restorative role by the angiogenesis and arteriogenesis. Understanding the basic mechanisms underlying functional recovery after cerebral stroke in aging subjects is likely to yield new insights into the treatment of brain injury in the clinic.

A bHLH-Based Feedback Loop Restricts Vascular Cell Proliferation in Plants.

Science.gov (United States)

Vera-Sirera, Francisco; De Rybel, Bert; Úrbez, Cristina; Kouklas, Evangelos; Pesquera, Marta; Álvarez-Mahecha, Juan Camilo; Minguet, Eugenio G; Tuominen, Hannele; Carbonell, Juan; Borst, Jan Willem; Weijers, Dolf; Blázquez, Miguel A

2015-11-23

Control of tissue dimensions in multicellular organisms requires the precise quantitative regulation of mitotic activity. In plants, where cells are immobile, tissue size is achieved through control of both cell division orientation and mitotic rate. The bHLH transcription factor heterodimer formed by target of monopteros5 (TMO5) and lonesome highway (LHW) is a central regulator of vascular width-increasing divisions. An important unanswered question is how its activity is limited to specify vascular tissue dimensions. Here we identify a regulatory network that restricts TMO5/LHW activity. We show that thermospermine synthase ACAULIS5 antagonizes TMO5/LHW activity by promoting the accumulation of SAC51-LIKE (SACL) bHLH transcription factors. SACL proteins heterodimerize with LHW-therefore likely competing with TMO5/LHW interactions-prevent activation of TMO5/LHW target genes, and suppress the over-proliferation caused by excess TMO5/LHW activity. These findings connect two thus-far disparate pathways and provide a mechanistic understanding of the quantitative control of vascular tissue growth. Copyright © 2015 Elsevier Inc. All rights reserved.

Plant metabolism and cell wall formation in space (microgravity) and on Earth

Science.gov (United States)

Lewis, Norman G.

1994-01-01

Variations in cell wall chemistry provide vascular plants with the ability to withstand gravitational forces, as well as providing facile mechanisms for correctional responses to various gravitational stimuli, e.g., in reaction wood formation. A principal focus of our current research is to precisely and systematically dissect the essentially unknown mechanism(s) of vascular plant cell wall assembly, particularly with respect to formation of its phenolic constituents, i.e., lignins and suberins, and how gravity impacts upon these processes. Formation of these phenolic polymers is of particular interest, since it appears that elaboration of their biochemical pathways was essential for successful land adaptation. By extrapolation, we are also greatly intrigued as to how the microgravity environment impacts upon 'normal' cell wall assembly mechanisms/metabolism.

Nicotinamide inhibits vasculogenic mimicry, an alternative vascularization pathway observed in highly aggressive melanoma.

Directory of Open Access Journals (Sweden)

Orit Itzhaki

Full Text Available Vasculogenic mimicry (VM describes functional vascular channels composed only of tumor cells and its presence predicts poor prognosis in melanoma patients. Inhibition of this alternative vascularization pathway might be of clinical importance, especially as several anti-angiogenic therapies targeting endothelial cells are largely ineffective in melanoma. We show the presence of VM structures histologically in a series of human melanoma lesions and demonstrate that cell cultures derived from these lesions form tubes in 3D cultures ex vivo. We tested the ability of nicotinamide, the amide form of vitamin B3 (niacin, which acts as an epigenetic gene regulator through unique cellular pathways, to modify VM. Nicotinamide effectively inhibited the formation of VM structures and destroyed already formed ones, in a dose-dependent manner. Remarkably, VM formation capacity remained suppressed even one month after the complete withdrawal of Nicotimamid. The inhibitory effect of nicotinamide on VM formation could be at least partially explained by a nicotinamide-driven downregulation of vascular endothelial cadherin (VE-Cadherin, which is known to have a central role in VM. Further major changes in the expression profile of hundreds of genes, most of them clustered in biologically-relevant clusters, were observed. In addition, nicotinamide significantly inhibited melanoma cell proliferation, but had an opposite effect on their invasion capacity. Cell cycle analysis indicated moderate changes in apoptotic indices. Therefore, nicotinamide could be further used to unravel new biological mechanisms that drive VM and tumor progression. Targeting VM, especially in combination with anti-angiogenic strategies, is expected to be synergistic and might yield substantial anti neoplastic effects in a variety of malignancies.

Preparation and features of polycaprolactone vascular grafts with the incorporated vascular endothelial growth factor

Energy Technology Data Exchange (ETDEWEB)

Sevostyanova, V. V., E-mail: sevostyanova.victoria@gmail.com; Khodyrevskaya, Y. I.; Glushkova, T. V.; Antonova, L. V.; Kudryavtseva, Y. A.; Barbarash, O. L.; Barbarash, L. S. [Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo (Russian Federation)

2015-10-27

The development of tissue-engineered small-diameter vascular grafts is an urgent issue in cardiovascular surgery. In this study, we assessed how the incorporation of the vascular endothelial growth factor (VEGF) affects morphological and mechanical properties of polycaprolactone (PCL) vascular grafts along with its release kinetics. Vascular grafts were prepared using two-phase electrospinning. In pursuing our aims, we performed scanning electron microscopy, mechanical testing, and enzyme-linked immunosorbent assay. Our results demonstrated the preservation of a highly porous structure and improvement of PCL/VEGF scaffold mechanical properties as compared to PCL grafts. A prolonged VEGF release testifies the use of this construct as a scaffold for tissue-engineered vascular grafts.

Limited farsightedness in network formation

NARCIS (Netherlands)

Morbitzer, D.T.

2013-01-01

Social relationships can be beneficial for various reasons. For example, people find jobs through their social contacts, and researchers connect with each other to cooperate on projects. Within these networks of relations, actors maintain different positions, which can influence their outcomes.

A Hepatic GAbp-AMPK Axis Links Inflammatory Signaling to Systemic Vascular Damage

Directory of Open Access Journals (Sweden)

Katharina Niopek

2017-08-01

Full Text Available Increased pro-inflammatory signaling is a hallmark of metabolic dysfunction in obesity and diabetes. Although both inflammatory and energy substrate handling processes represent critical layers of metabolic control, their molecular integration sites remain largely unknown. Here, we identify the heterodimerization interface between the α and β subunits of transcription factor GA-binding protein (GAbp as a negative target of tumor necrosis factor alpha (TNF-α signaling. TNF-α prevented GAbpα and β complex formation via reactive oxygen species (ROS, leading to the non-energy-dependent transcriptional inactivation of AMP-activated kinase (AMPK β1, which was identified as a direct hepatic GAbp target. Impairment of AMPKβ1, in turn, elevated downstream cellular cholesterol biosynthesis, and hepatocyte-specific ablation of GAbpα induced systemic hypercholesterolemia and early macro-vascular lesion formation in mice. As GAbpα and AMPKβ1 levels were also found to correlate in obese human patients, the ROS-GAbp-AMPK pathway may represent a key component of a hepato-vascular axis in diabetic long-term complications.

STRUCTURAL BASIS OF THE VASCULAR HEMOSTATIC MECHANISM IN THE UTERINE CERVIX.

Science.gov (United States)

Prokopchook-Lyckbäck, Alexander V

2015-01-01

The objective of the study was to investigate the angioarchitectonics and the functional morphology of the vessels of the cervix and to clarify the role of structural features of these vessels in preventing hemorrhaging in parturition during cervical dilatation. Cervixes uteri were obtained from corpses of 30 women of various ages and 5 ablated at labor. Series of histotopographical specimens of the cervixes were processed using histological and histochemical methods. Peculiar features of the angioarchitectonics, histotopography and structure of cervical vessels were encountered. Arteries penetrating the cervix are surrounded by tight muffs of anastomizing veins that are closely adjacent to the arteries. In other cases, the arteries are located within the lumen of veins--"vessels within vessels". Cervical arteries make up subendocervical convolutions. During pregnancy, smooth muscle "cushions" develop in the vessels. The cervix is pierced by a network of veins that divide the cervical tissue into separate stromal "lobules". This peculiar vascular architecture might be important structural basis of the vascular hemostatic mechanism in the neck of the uterus triggered by labor. It prevents vessel rupture, hemorrhaging and amniotic fluid and air embolism during cervical dilatation. The venous network that passes through the cervix makes it easy for the separate stromal "lobules" of the cervix to move relative to each other during cervical dilatation.

Paracrine control of vascularization and neurogenesis by neurotrophins.

Science.gov (United States)

Emanueli, Costanza; Schratzberger, Peter; Kirchmair, Rudolf; Madeddu, Paolo

2003-10-01

The neuronal system plays a fundamental role in the maturation of primitive embryonic vascular network by providing a paracrine template for blood vessel branching and arterial differentiation. Furthermore, postnatal vascular and neural regeneration cooperate in the healing of damaged tissue. Neurogenesis continues in adulthood although confined to specific brain regions. Following ischaemic insult, neural staminal cells contribute towards the healing process through the stimulation of neurogenesis and vasculogenesis. Evidence indicates that nerves and blood vessels exert a reciprocal control of their own growth by paracrine mechanisms. For instance, guidance factors, including vascular endothelial growth factor A (VEGF-A) and semaphorins, which share the ability of binding neuropilin receptors, play a pivotal role in the tridimensional growth pattern of arterial vessels and nerves. Animal models and clinical studies have demonstrated a role of VEGF-A in the pathogenesis of ischaemic and diabetic neuropathies. Further, supplementation with VEGF-A ameliorates neuronal recovery by exerting protective effects on nerves and stimulating reparative neovascularization. Human tissue kallikrein, a recently discovered angiogenic and arteriogenic factor, accelerates neuronal recovery by stimulating the growth of vasa nervorum. Conversely, the neurotrophin nerve growth factor, known to regulate neuronal survival and differentiation, is now regarded as a stimulator of angiogenesis and arteriogenesis. These results indicate that angiogenesis and neurogenesis are paracrinally regulated by growth factors released by endothelial cells and neurons. Supplementation of these growth factors, alone or in combination, could benefit the treatment of ischaemic diseases and neuropathies.

Double-filter identification of vascular-expressed genes using Arabidopsis plants with vascular hypertrophy and hypotrophy.

Science.gov (United States)

Ckurshumova, Wenzislava; Scarpella, Enrico; Goldstein, Rochelle S; Berleth, Thomas

2011-08-01

Genes expressed in vascular tissues have been identified by several strategies, usually with a focus on mature vascular cells. In this study, we explored the possibility of using two opposite types of altered tissue compositions in combination with a double-filter selection to identify genes with a high probability of vascular expression in early organ primordia. Specifically, we generated full-transcriptome microarray profiles of plants with (a) genetically strongly reduced and (b) pharmacologically vastly increased vascular tissues and identified a reproducible cohort of 158 transcripts that fulfilled the dual requirement of being underrepresented in (a) and overrepresented in (b). In order to assess the predictive value of our identification scheme for vascular gene expression, we determined the expression patterns of genes in two unbiased subsamples. First, we assessed the expression patterns of all twenty annotated transcription factor genes from the cohort of 158 genes and found that seventeen of the twenty genes were preferentially expressed in leaf vascular cells. Remarkably, fifteen of these seventeen vascular genes were clearly expressed already very early in leaf vein development. Twelve genes with published leaf expression patterns served as a second subsample to monitor the representation of vascular genes in our cohort. Of those twelve genes, eleven were preferentially expressed in leaf vascular tissues. Based on these results we propose that our compendium of 158 genes represents a sample that is highly enriched for genes expressed in vascular tissues and that our approach is particularly suited to detect genes expressed in vascular cell lineages at early stages of their inception. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Microarray Data Analysis of Space Grown Arabidopsis Leaves for Genes Important in Vascular Patterning. Analysis of Space Grown Arabidopsis with Microarray Data from GeneLab: Identification of Genes Important in Vascular Patterning

Science.gov (United States)

Weitzel, A. J.; Wyatt, S. E.; Parsons-Wingerter, P.

2016-01-01

Venation patterning in leaves is a major determinant of photosynthesis efficiency because of its dependency on vascular transport of photo-assimilates, water, and minerals. Arabidopsis thaliana grown in microgravity show delayed growth and leaf maturation. Gene expression data from the roots, hypocotyl, and leaves of A. thaliana grown during spaceflight vs. ground control analyzed by Affymetrix microarray are available through NASA's GeneLab (GLDS-7). We analyzed the data for differential expression of genes in leaves resulting from the effects of spaceflight on vascular patterning. Two genes were found by preliminary analysis to be up-regulated during spaceflight that may be related to vascular formation. The genes are responsible for coding an ARGOS (Auxin-Regulated Gene Involved in Organ Size)-like protein (potentially affecting cell elongation in the leaves), and an F-box/kelch-repeat protein (possibly contributing to protoxylem specification). Further analysis that will focus on raw data quality assessment and a moderated t-test may further confirm up-regulation of the two genes and/or identify other gene candidates. Plants defective in these genes will then be assessed for phenotype by the mapping and quantification of leaf vascular patterning by NASA's VESsel GENeration (VESGEN) software to model specific vascular differences of plants grown in spaceflight.

Large scale serial two-photon microscopy to investigate local vascular changes in whole rodent brain models of Alzheimer's disease

Science.gov (United States)

Delafontaine-Martel, P.; Lefebvre, J.; Damseh, R.; Castonguay, A.; Tardif, P.; Lesage, F.

2018-02-01

In this study, an automated serial two-photon microscope was used to image a fluorescent gelatin filled rodent's brain in 3D. A method to compute vascular density using automatic segmentation was combined with coregistration techniques to build group-level vasculature metrics. By studying the medial prefrontal cortex and the hippocampal formation of 3 age groups (2, 4.5 and 8 months old), we compared vascular density for both WT and an Alzheimer model transgenic brain (APP/PS1). We observe a loss of vascular density caused by the ageing process and we propose further analysis to confirm our results.

Retrospective Study on Laser Treatment of Oral Vascular Lesions Using the "Leopard Technique": The Multiple Spot Irradiation Technique with a Single-Pulsed Wave.

Science.gov (United States)

Miyazaki, Hidetaka; Ohshiro, Takafumi; Romeo, Umberto; Noguchi, Tadahide; Maruoka, Yutaka; Gaimari, Gianfranco; Tomov, Georgi; Wada, Yoshitaka; Tanaka, Kae; Ohshiro, Toshio; Asamura, Shinichi

2018-06-01

This study aimed to retrospectively evaluate the efficacy and safety of laser treatment of oral vascular lesions using the multiple spot irradiation technique with a single-pulsed wave. In laser therapy for vascular lesions, heat accumulation induced by excessive irradiation can cause adverse events postoperatively, including ulcer formation, resultant scarring, and severe pain. To prevent heat accumulation and side effects, we have applied a multiple pulsed spot irradiation technique, the so-called "leopard technique" (LT) to oral vascular lesions. This approach was originally proposed for laser treatment of nevi. It can avoid thermal concentration at the same spot and spare the epithelium, which promotes smooth healing. The goal of the study was to evaluate this procedure and treatment outcomes. The subjects were 46 patients with 47 oral vascular lesions treated with the LT using a Nd:YAG laser (1064 nm), including 24 thick lesions treated using a combination of the LT and intralesional photocoagulation. All treatment outcomes were satisfactory without serious complications such as deep ulcer formation, scarring, bleeding, or severe swelling. Laser therapy with the LT is a promising less-invasive treatment for oral vascular lesions.

Divergent effects of 17-{beta}-estradiol on human vascular smooth muscle and endothelial cell function diminishes TNF-{alpha}-induced neointima formation

Energy Technology Data Exchange (ETDEWEB)

Nintasen, Rungrat [Division of Cardiovascular Medicine, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT (United Kingdom); Multidisciplinary Cardiovascular Research Center (MCRC), University of Leeds, Leeds LS2 9JT (United Kingdom); Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University (Thailand); Riches, Kirsten; Mughal, Romana S. [Division of Cardiovascular Medicine, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT (United Kingdom); Multidisciplinary Cardiovascular Research Center (MCRC), University of Leeds, Leeds LS2 9JT (United Kingdom); Viriyavejakul, Parnpen; Chaisri, Urai; Maneerat, Yaowapa [Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University (Thailand); Turner, Neil A. [Division of Cardiovascular Medicine, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT (United Kingdom); Multidisciplinary Cardiovascular Research Center (MCRC), University of Leeds, Leeds LS2 9JT (United Kingdom); Porter, Karen E., E-mail: medkep@leeds.ac.uk [Division of Cardiovascular Medicine, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT (United Kingdom); Multidisciplinary Cardiovascular Research Center (MCRC), University of Leeds, Leeds LS2 9JT (United Kingdom)

2012-04-20

Highlights: Black-Right-Pointing-Pointer TNF-{alpha} augments neointimal hyperplasia in human saphenous vein. Black-Right-Pointing-Pointer TNF-{alpha} induces detrimental effects on endothelial and smooth muscle cell function. Black-Right-Pointing-Pointer Estradiol exerts modulatory effects on TNF-induced vascular cell functions. Black-Right-Pointing-Pointer The modulatory effects of estradiol are discriminatory and cell-type specific. -- Abstract: Coronary heart disease (CHD) is a condition characterized by increased levels of proinflammatory cytokines, including tumor necrosis factor-{alpha} (TNF-{alpha}). TNF-{alpha} can induce vascular endothelial cell (EC) and smooth muscle cell (SMC) dysfunction, central events in development of neointimal lesions. The reduced incidence of CHD in young women is believed to be due to the protective effects of estradiol (E2). We therefore investigated the effects of TNF-{alpha} on human neointima formation and SMC/EC functions and any modulatory effects of E2. Saphenous vein (SV) segments were cultured in the presence of TNF-{alpha} (10 ng/ml), E2 (2.5 nM) or both in combination. Neointimal thickening was augmented by incubation with TNF-{alpha}, an effect that was abolished by co-culture with E2. TNF-{alpha} increased SV-SMC proliferation in a concentration-dependent manner that was optimal at 10 ng/ml (1.5-fold increase), and abolished by E2 at all concentrations studied (1-50 nM). Surprisingly, E2 itself at low concentrations (1 and 5 nM) stimulated SV-SMC proliferation to a level comparable to that of TNF-{alpha} alone. SV-EC migration was significantly impaired by TNF-{alpha} (42% of control), and co-culture with E2 partially restored the ability of SV-EC to migrate and repair the wound. In contrast, TNF-{alpha} increased SV-SMC migration by 1.7-fold, an effect that was completely reversed by co-incubation with E2. Finally, TNF-{alpha} potently induced ICAM-1 and VCAM-1 expression in both SV-EC and SV-SMC. However there

Vascular abnormalities associated with acute hypoxia in human melanoma xenografts

International Nuclear Information System (INIS)

Simonsen, Trude G.; Gaustad, Jon-Vidar; Leinaas, Marit N.; Rofstad, Einar K.

2012-01-01

Background and purpose: The fraction of hypoxic cells has been shown to differ substantially among human tumors of the same histological type. In this study, a window chamber model was used to identify possible mechanisms leading to the development of highly different hypoxic fractions in A-07 and R-18 human melanoma xenografts. Materials and methods: Chronic and acute hypoxia was assessed in intradermal tumors using an immunohistochemical and a radiobiological assay. Functional and morphological parameters of the vascular networks of tumors growing in dorsal window chambers were assessed with intravital microscopy. Results: R-18 tumors showed significantly higher hypoxic fractions than A-07 tumors, and the difference was mostly due to acute hypoxia. Compared to A-07 tumors, R-18 tumors showed low vascular densities, low vessel diameters, long vessel segments, low blood flow velocities, frequent fluctuations in blood flow, and a high fraction of narrow vessels with absent or very low and varying flux of red blood cells. Conclusion: The high fraction of acute hypoxia in R-18 tumors was a consequence of frequent fluctuations in blood flow and red blood cell flux combined with low vascular density. The fluctuations were most likely caused by high geometric resistance to blood flow in the tumor microvasculature.

Interferences between Sphagnum and vascular plants: effects on plant community structure and peat formation

OpenAIRE

Malmer, Nils; Albinsson, C; Svensson, B M; Wallén, Bo

2003-01-01

The interference between vascular plants and peat mosses with respect to nitrogen and phosphorus was studied in a fertilization experiment and with respect to competition for light in a removal experiment in poor fens with either soligenous or topogenous hydrology using Narthecium ossifragum (L.) Huds. and three species of Sphagnum sect. Sphagnum as targets. Adding fertilizer either on the moss surface or below it confirmed the hypotheses of an asymmetric competition for nutrients, viz. that ...

Proatherogenic pathways leading to vascular calcification

International Nuclear Information System (INIS)

Mazzini, Michael J.; Schulze, P. Christian

2006-01-01

Cardiovascular disease is the leading cause of morbidity and mortality in the western world and atherosclerosis is the major common underlying disease. The pathogenesis of atherosclerosis involves local vascular injury, inflammation and oxidative stress as well as vascular calcification. Vascular calcification has long been regarded as a degenerative process leading to mineral deposition in the vascular wall characteristic for late stages of atherosclerosis. However, recent studies identified vascular calcification in early stages of atherosclerosis and its occurrence has been linked to clinical events in patients with cardiovascular disease. Its degree correlates with local vascular inflammation and with the overall impact and the progression of atherosclerosis. Over the last decade, diverse and highly regulated molecular signaling cascades controlling vascular calcification have been described. Local and circulating molecules such as osteopontin, osteoprogerin, leptin and matrix Gla protein were identified as critical regulators of vascular calcification. We here review the current knowledge on molecular pathways of vascular calcification and their relevance for the progression of cardiovascular disease

BOLD Granger causality reflects vascular anatomy.

Directory of Open Access Journals (Sweden)

J Taylor Webb

Full Text Available A number of studies have tried to exploit subtle phase differences in BOLD time series to resolve the order of sequential activation of brain regions, or more generally the ability of signal in one region to predict subsequent signal in another region. More recently, such lag-based measures have been applied to investigate directed functional connectivity, although this application has been controversial. We attempted to use large publicly available datasets (FCON 1000, ADHD 200, Human Connectome Project to determine whether consistent spatial patterns of Granger Causality are observed in typical fMRI data. For BOLD datasets from 1,240 typically developing subjects ages 7-40, we measured Granger causality between time series for every pair of 7,266 spherical ROIs covering the gray matter and 264 seed ROIs at hubs of the brain's functional network architecture. Granger causality estimates were strongly reproducible for connections in a test and replication sample (n=620 subjects for each group, as well as in data from a single subject scanned repeatedly, both during resting and passive video viewing. The same effect was even stronger in high temporal resolution fMRI data from the Human Connectome Project, and was observed independently in data collected during performance of 7 task paradigms. The spatial distribution of Granger causality reflected vascular anatomy with a progression from Granger causality sources, in Circle of Willis arterial inflow distributions, to sinks, near large venous vascular structures such as dural venous sinuses and at the periphery of the brain. Attempts to resolve BOLD phase differences with Granger causality should consider the possibility of reproducible vascular confounds, a problem that is independent of the known regional variability of the hemodynamic response.

Modeling of Kidney Hemodynamics: Probability-Based Topology of an Arterial Network

DEFF Research Database (Denmark)

Postnov, Dmitry D; Marsh, Donald J; Postnov, Dmitry E

2016-01-01

CT) data we develop an algorithm for generating the renal arterial network. We then introduce a mathematical model describing blood flow dynamics and nephron to nephron interaction in the network. The model includes an implementation of electrical signal propagation along a vascular wall. Simulation...

Human in vitro 3D co-culture model to engineer vascularized bone-mimicking tissues combining computational tools and statistical experimental approach.

Science.gov (United States)

Bersini, Simone; Gilardi, Mara; Arrigoni, Chiara; Talò, Giuseppe; Zamai, Moreno; Zagra, Luigi; Caiolfa, Valeria; Moretti, Matteo

2016-01-01

The generation of functional, vascularized tissues is a key challenge for both tissue engineering applications and the development of advanced in vitro models analyzing interactions among circulating cells, endothelium and organ-specific microenvironments. Since vascularization is a complex process guided by multiple synergic factors, it is critical to analyze the specific role that different experimental parameters play in the generation of physiological tissues. Our goals were to design a novel meso-scale model bridging the gap between microfluidic and macro-scale studies, and high-throughput screen the effects of multiple variables on the vascularization of bone-mimicking tissues. We investigated the influence of endothelial cell (EC) density (3-5 Mcells/ml), cell ratio among ECs, mesenchymal stem cells (MSCs) and osteo-differentiated MSCs (1:1:0, 10:1:0, 10:1:1), culture medium (endothelial, endothelial + angiopoietin-1, 1:1 endothelial/osteo), hydrogel type (100%fibrin, 60%fibrin+40%collagen), tissue geometry (2 × 2 × 2, 2 × 2 × 5 mm(3)). We optimized the geometry and oxygen gradient inside hydrogels through computational simulations and we analyzed microvascular network features including total network length/area and vascular branch number/length. Particularly, we employed the "Design of Experiment" statistical approach to identify key differences among experimental conditions. We combined the generation of 3D functional tissue units with the fine control over the local microenvironment (e.g. oxygen gradients), and developed an effective strategy to enable the high-throughput screening of multiple experimental parameters. Our approach allowed to identify synergic correlations among critical parameters driving microvascular network development within a bone-mimicking environment and could be translated to any vascularized tissue. Copyright © 2015 Elsevier Ltd. All rights reserved.

POLYMORPHISM OF THE SYNDROME OF HYPERACTIVE URINARY BLADDER IN PATIENTS WITH ACUTE AND CHRONIC VASCULAR DISEASES OF THE BRAIN

Directory of Open Access Journals (Sweden)

P. G. Shvarts

2016-01-01

Full Text Available Abstract. The paper discusses the main etiological, phenomenological and pathogenetic mechanisms of forming the syndrome of overactive bladder (OAB in patients with acute and chronic cerebrovascular diseases. Describes the role of melatonin, arginine vasopressin (AVP and corticotropin-releasing factor hormone (CRFH in maintaining the rhythms of urination, urine formation and retention of urine in norm and abnormalities in these systems in acute and chronic vascular pathology of the brain. Described phenomenology OAB syndrome in vascular diseases of the brain. Shows a differentiated approach to pharmacological correction in patients with different clinical variants of urinary disorders and urine formation in the framework of the OAB syndrome with the use of neurotransmitter therapy and hormonesensitive.

Vascular Remodeling in Experimental Hypertension

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Norma R. Risler

2005-01-01

Full Text Available The basic hemodynamic abnormality in hypertension is an increased peripheral resistance that is due mainly to a decreased vascular lumen derived from structural changes in the small arteries wall, named (as a whole vascular remodeling. The vascular wall is an active, flexible, and integrated organ made up of cellular (endothelial cells, smooth muscle cells, adventitia cells, and fibroblasts and noncellular (extracellular matrix components, which in a dynamic way change shape or number, or reorganize in response to physiological and pathological stimuli, maintaining the integrity of the vessel wall in physiological conditions or participating in the vascular changes in cardiovascular diseases such as hypertension. Research focused on new signaling pathways and molecules that can participate in the mechanisms of vascular remodeling has provided evidence showing that vascular structure is not only affected by blood pressure, but also by mechanisms that are independent of the increased pressure. This review will provide an overview of the evidence, explaining some of the pathophysiologic mechanisms participating in the development of the vascular remodeling, in experimental models of hypertension, with special reference to the findings in spontaneously hypertensive rats as a model of essential hypertension, and in fructose-fed rats as a model of secondary hypertension, in the context of the metabolic syndrome. The understanding of the mechanisms producing the vascular alterations will allow the development of novel pharmacological tools for vascular protection in hypertensive disease.

Obesity-induced vascular dysfunction and arterial stiffening requires endothelial cell arginase 1.

Science.gov (United States)

Bhatta, Anil; Yao, Lin; Xu, Zhimin; Toque, Haroldo A; Chen, Jijun; Atawia, Reem T; Fouda, Abdelrahman Y; Bagi, Zsolt; Lucas, Rudolf; Caldwell, Ruth B; Caldwell, Robert W

2017-11-01

Elevation of arginase activity has been linked to vascular dysfunction in diabetes and hypertension by a mechanism involving decreased nitric oxide (NO) bioavailability due to L-arginine depletion. Excessive arginase activity also can drive L-arginine metabolism towards the production of ornithine, polyamines, and proline, promoting proliferation of vascular smooth muscle cells and collagen formation, leading to perivascular fibrosis. We hypothesized that there is a specific involvement of arginase 1 expression within the vascular endothelial cells in this pathology. To test this proposition, we used models of type 2 diabetes and metabolic syndrome. Studies were performed using wild type (WT), endothelial-specific arginase 1 knockout (EC-A1-/-) and littermate controls(A1con) mice fed high fat-high sucrose (HFHS) or normal diet (ND) for 6 months and isolated vessels exposed to palmitate-high glucose (PA/HG) media. Some WT mice or isolated vessels were treated with an arginase inhibitor, ABH [2-(S)-amino-6-boronohexanoic acid. In WT mice, the HFHS diet promoted increases in body weight, fasting blood glucose, and post-prandial insulin levels along with arterial stiffening and fibrosis, elevated blood pressure, decreased plasma levels of L-arginine, and elevated L-ornithine. The HFHS diet or PA/HG treatment also induced increases in vascular arginase activity along with oxidative stress, reduced vascular NO levels, and impaired endothelial-dependent vasorelaxation. All of these effects except obesity and hypercholesterolemia were prevented or significantly reduced by endothelial-specific deletion of arginase 1 or ABH treatment. Vascular dysfunctions in diet-induced obesity are prevented by deletion of arginase 1 in vascular endothelial cells or arginase inhibition. These findings indicate that upregulation of arginase 1 expression/activity in vascular endothelial cells has an integral role in diet-induced cardiovascular dysfunction and metabolic syndrome. Published

Creation of a Bioengineered Skin Flap Scaffold with a Perfusable Vascular Pedicle.

Science.gov (United States)

Jank, Bernhard J; Goverman, Jeremy; Guyette, Jacques P; Charest, Jon M; Randolph, Mark; Gaudette, Glenn R; Gershlak, Joshua R; Purschke, Martin; Javorsky, Emilia; Nazarian, Rosalynn M; Leonard, David A; Cetrulo, Curtis L; Austen, William G; Ott, Harald C